(navigation image)
Home American Libraries | Canadian Libraries | Universal Library | Community Texts | Project Gutenberg | Children's Library | Biodiversity Heritage Library | Additional Collections
Search: Advanced Search
Anonymous User (login or join us)
Upload
See other formats

Full text of "Harvard medical alumni bulletin"

iAUTUMN 2008 




ALUMNI BULLETIN 



f-ji^ 



THE 

MEMORY 

ISSUE 



^v- 






^^ 



Selection is the very keel 
on which our mental ship 
is built. And in the case of 
memory its utihty is obvious. 
If w^e remembered every- 
thing, v^^e should on most 
occasions be as ill off as if 
v^e remembered nothing. 

— William James, Class of 1859 




AUTUMN 2008 • VOLUME 82, NUMBER 1 



CONT 



DEPARTMENTS 



Letters 3 

Pulse 4 

Members of the Class of 2008 meet 
their match; Harvard Catalyst helps 
connect the docs 

President's Report 7 

hy Steven E. Weinberger 

Bookshelf 8 

Bookmark 

A review by Elissa Ely of Spiritual 
Evolution: A Scientific Defense of Faith 

Benchmarks 10 

More pieces to the Alzheimer's puzzle 

Class Notes 56 

I n Memoriom 59 

Edmund Sonnenhlick 

Obituaries 60 

Endnotes 64 

A surgeon remembers his time with 
Albert Schweitzer, hy Robert M. Goldwyn 





The Still Small Voice 46 

A severely burned child teaches his 
surgeon about the enduring power of 
the spirit, hy Allan]. Hamilton 

Fever Pitch 52 

A physician recalls his work in a 
World War II research project aimed 
at stamping out malaria, hy Curtis Prout 

Cover image: John Lund/Riser/Getty Images 



SPECIAL REPORT: THE MEMORY ISSUE 



iZ As iirtlG U06S by Our brains make, hold, and lose memories in 
response to changes wrought by age. by ann marie menting 

18 What Tangled Webs People with Alzheimer's disease tend to 

weave modifications into their memories, fcy Andrew e. budson 

22 Perish the Thought what happens when memories are too 
painful to bear? fc^/jEssicA cerretani 

26 Memory Upgrade Despite a wealth of brain boosters on the market, 
a psychiatrist remains a frugal shopper, hy elissa ely 

oU Inink Nothing Ot It one prescription for keeping the brain active 
may be quite simple: meditate. byjEssicA cerretani 

32 Memory Splat Mat Take the seven Dwarf Challenge to test 
your wits. fo^AiicE flaherty 

34 Mind Games when it comes to building a better brain, 
sometimes play's the thing, hy majid fotuhi 

36 Dream Weaver The best advice for optimal memory? Sleep on it. 

by JESSICA CERRETANI 

o" KeCall buttons combat retention deficit disorder with these tips. 

b)- AARON P. NELSON 

41 bpeak, IvlemOry Bearing witness fosters heahng among survivors 
of childhood sexual abuse. byjuoiTH lewis herman 



Harv^rrl MeHTral 



ALUMNI BULLETIN 




In This Issue 

OON AFTER DR. WATSON AND SHERLOCK HOLMES BECAME ROOMMATES, THE 

physician had occasion to mention to the detective that the earth 
revolves around the sun. This information was unwelcome to the lat- 
ter, who promptly said, "Now that I do know it I shall do my best to forget it." 
Holmes then elaborated: "I consider that a man's brain originally is like a little 
empty attic, and you have to stock it with such furniture as you choose. A fool 
takes in all the lumber of every sort that he comes across, so that the knowl- 
edge which might be useful to him gets crowded out . . . [and] he has difficulty 
in laying his hands upon it." 

I read A Study in Scarlet well over 50 years ago and remember only this pas- 
sage, a bit of lumber that thumped to the floor of my brain at the time and has 
never been swept away, whereas all the rest — the story itself— has been vacu- 
umed off. Why this snippet persisted in memory I don't know. I was in school, 
and perhaps some small part of my amygdala was aroused by the horrifying 
thought that my efforts to conjugate Latin verbs, sort out the faults of Franklin 
Pierce from those of James Buchanan, or come to terms with pi bonds were a 
fool's errand. In any event, I have come to realize that I am not the custodian of 
my own attic. 

Holmes had it partly right, although the attic may be a great deal bigger than 
he surmised and its conscious management more difficult. There are people, 
very few of them, who live with a vivid, day-by-day mental chronicle of their 
lives and can say in a moment what they were wearing on September 14, 1982, 
or, reversing the task, tell you on what date Princess Grace died. This ability 
does, however, seem to drain off some of the brain's reserves. None of the 
knov^m people with this hyperthymestic syndrome has led a life of otherwise 
remarkable accomplishment. 

Perhaps it is forgetting, not remembering, then, that we should cultivate, and 
having good filters is what we should aspire to. As George Eliot wrote, "If we 
had a keen vision and feeling of all ordinary human life, it would be like hear- 
ing the grass grow and the squirrel's heart beat, and we should die of that roar 
which lies on the other side of silence. As it is, the quickest of us walk about 
well wadded with stupidity." 



Mj^6ua\ I/Va j^U^-e/^ 



EDITOR-IN-CHIEF 

WiUiam Ira Bennett '68 

EDITOR 

Paula Brewer Byron 

ASSOCIATE EDITOR 

Arm Marie Menting 

ASSISTANT EDITOR 

Jessica Cerretani 

EDITORIAL INTERNS 

Ryann Burnett 
Kathleen Preston 

BOOK REVIEW EDITOR 

EUssa Ely '88 



EDITORIAL BOARD 

Judy Ann Bigby '78 

Rafael Campo '92 

EUssa Ely '88 

Daniel D. Federman '53 

Timothy G. Ferris '92 

Ahce Flaherty '94 

Atul Gawande '94 

Robert M. Goldwyn '56 

Petri Klass '86 

Victoria McEvoy '75 

James J. O'Connell '82 

Nancy E. Oriol '79 

Anthony S. Patton '58 

Mitchell T. Rabkin '55 

Jason Sanders '08 

Eleanor Shore '55 



DESIGN DIRECTOR 

Laura McFadden 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



ASSOCIATION OFFICERS 

Steven E. Weinberger '73, president 

JudyArm Bigby '78, president-elect 1 

Gilbert Omenn '65, president-elect 2 

Ken Offit '81, vice president 

NeO R. Powe '80, secretary 

Douglas G. Kelling '72, treasurer 

COUNCILLORS 

H. Thomas Aretz '76 

Rosa M. Crum '85 
Laurie GlLmcher '76 

Jim Yong Kim '86 

Triste N. Lieteau '98 

Eileen Reynolds '90 

Michael Rosenblatt '73 

Rahul Sakhuja '03 
John D. Stoeckle '47 

CHAIRMAN OF ALUMNI RELATIONS 

George E. Thibault '69 

REPRESENTATIVES TO THE 
HARVARD ALUMNI ASSOCIATION 

Joseph K.Hurd, Jr. '64 
John D. Stoeckle '47 

The Harvard Medical Mumni Bulletin is 

pubhshed three times a year at 

25 Shattuck Street, Boston, MA 02115. 

© Harvard Medical Alumni Association 

Phone: 617-384-8900 • Fax: 617-384-8901 

Email: bulletin@hms.harvard.edu 

Web: http://alumnibulletin.med.harvard.edu 

Third class postage paid at Boston, 

Massachusetts. Postmaster, send form 3579 

to 25 Shattuck Street, Boston, MA 02115 

ISSN 0191-7757 • Printed in the U.SA. 



SECOND OPINIONS FROM OUR READERS 



T.ETTERS^ 



Gator Aid 

We write to supplement the mention of 
Deborah German 76 in Ann Marie 
Menting's "The Dean Counter" in the 
Autumn 2007 issue. We strongly identify 
with Dr. German's characterization of the 
physicians she intends to educate and 
mentor in her role as dean of the new Col- 
lege of Medicine at the University of Cen- 
tral Florida. We are especially delighted 
because Nemours Childreris Hospital, a 
new pediatric specialty facility will be 
located near the medical school. We hope 
that as the hospital becomes part of Cen- 
tral Florida's expanding health services 
resources, we will be able to make a solid 
contribution to the "good doctors" that 
Dr. German will help nurture. We wish 
her the best and applaud her for being 
more fearful of not pursuing this impor- 
tant goal than she is of failure. 

DAVID J. BAILEY, MD, MBA, 

THE NEMOURS FOUNDATION 
JOHN NOSEWORTHY '70, FACS, FAAP, 

THE NEMOURS PARTNERSHIP FOR 

CHILDREN'S HEALTH 
JACKSONVILLE, FLORIDA 

Spreading the Health 

In response to "The Dean Counter," I'm 
proud to share the story of one of your 
alumni. In 1978, Rodolfo Herrera 
Llerandi '42 founded the Universidad 
Francisco Marroquin Medical School in 
Guatemala with the same mission as 
HMS; to seek excellence. By doing this. 
Dr. Herrera, now emeritus dean, was able 
to transfer the skills of his hands to the 
hands of the more than 500 doctors who 
have since graduated from UFMMS. 

Dr. Herrera's leadership has shaped 
UFMMS into an institution that main- 
tains the high standards required to meet 
twenty- first century needs — a worthy 
goal for a "daughter" of HMS. Now 95 
years old. Dr. Herrera keeps inspiring us 
to pursue what doctors are for: to heal 
and support patients efficiently, respect- 
fully, and with love. 

RODRIGO BOY, MD 

GUATEMALA CITY, GUATEMALA 



BATTEN DOWN THE HATCHES 



Hai-varrl Merlical 




WHAT ARf DOCTORS FOR? 



"What Are Doctors For?" in the Autumn 2007 
issue of the Bulletin touched close to home. 
Nearly two years ago I ended my overtaxed 
primary care practice at Massachusetts Gener- 
al Hospital, where I was one of the two busiest 
general internists, and started Orchard Health 
Care, a membership practice that more effec- 
tively serves about one-quarter the number of 
patients I had previously. As part of that tran- 
sition, I rejoined the Beth Israel Deaconess net- 
work, which enthusiastically supports such 
"boutique" medical practices. 

The many patients who continued with me 
(and the new ones who joined) are pleased with the calmer and more 
detailed care and advice they receive. My staff is no longer frayed. I am no 
longer pressed so hard, nor do I have to move so quickly that I fear I will 
miss important medical data. I have regained my joy in the art and practice 
of medicine. 

I am acutely aware of the socioeconomic issues that membership practices 
raise, but I am more concerned about the economic starvation diet that a con- 
federation of insurers and govermnent regulators have forced on primary care 
for the past two decades. Primary care is dying. The shortage of primary care 
physicians is critical in Massachusetts and elsewhere — and no solution is in 
sight. Medical students, even those attracted to internal medicine, look to 
other specialties to receive fair compensation for their skills and to enjoy a 
reasonable life. For the ten years I precepted in the primary care clerkship at 
HMS, not one of the talented students I worked with went into primary care. 

My patients and I have escaped the shipwreck that primary care has 
become through the membership model, where patients pay me an annual 
fee so I can afford to see hundreds rather than thousands of patients. My 
earnings are now comparable to those of the average dermatologist or ortho- 
pedist. This is my micro-solution, but it is not a macro-solution for a core 
problem in U.S. medicine today: the demise of primary care. Where is our 
medical school on this issue? Where are the medical societies? 

Perhaps we want a care system built on nurse practitioners and "disease 
management" telephone staff collectively trying to replace the primary care 
role, an alternative that is inferior across the board on cost, quality, access, 
and patient satisfaction. The good ship primary care is foundering on eco- 
nomic rocks. Prompt action might save it. But more likely our studied igno- 
rance of the economic forces destroying primary care will continue, and 
we'll soon be looking around and asking what happened. We'll wonder why 
there are no primary care physicians, and why medical care has become 
more expensive, more disjointed, and less effective. 

HMS is a world leader in medical research and policy. It should take a dra- 
matically more active role in spothghting the disintegration of primary care 
and in promoting changes in the regulatory and economic pohcies that are 
destroying the keystone of our medical care system. 

STEVEN R. KANNER '69 
WALTHAM, MASSACHUSETTS 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



ptit.sk 



MAKING THE ROUNDS AT HMS 



The Envelope, Please 

ON THE 56TH ANNUAL MATCH DAY IN 

March, the 168 members of the HMS 
Class of 2008 gathered to receive their 
much-anticipated white envelopes — 
the contents of which revealed where 
the fourth-years would be spending the 
first year of their residencies. Nearly 
half the graduates have remained in 
Massachusetts for at least part of their 
residencies, while 23 percent have 
headed to California and 7 percent have 
gone to New York. Internal medicine 
remained the most popular specialty, 
with 27 percent of the class matching in 
this field. Pediatrics was the second 
most chosen specialty area. 




ANESTHESIOLOGY 

Arielle Cohen 

Mount Sinai Hospital, NYC 

Christina Coleman 

University of California- 
San Francisco 

Jored Feinman 

Hospital of tfie University of 
Pennsylvania, Pfiiladelpfiio 

Robert iyAeisner 

Brigfiam and Women's Hospital 

Noah Stites-Hallett 

University of California- 
San Francisco 

DERMATOLOGY 

Thomas Hocker 

Mayo School of Graduate 
Medical Education, 
Rocfiester, MN 

Patrick Safo 

University of Pittsburgh 
Medical Center 

Jessica Shin 

Massachusetts General Hospital 

Meeno Singh 

Mayo School of Graduate 
Medical Education, 
Rochester, MN 



Bryan Sun 

Stanford University Programs 

EMERGENCY MEDICINE 

Eric Ernster 

Harbor-UCIA Medical Center, 
Torrance, CA 

Priscilla Hanudel 

UCLA Medical Center 

Andre>v Herring 

Alameda County Medical Center, 
Oakland, CA 

Ziad Obermeyer 

Brigham and Women's Hospital 

Benjamin Orozco 

Hennepin County Medical 
Center, Minneapolis, MN 

Sarah Stewart 
de Ramirez 

Johns Hopkins Hospital 

FAMILY MEDICINE 

Elise Cheng 

O'Connor Hospital, 
San Jose, CA 

Kimberly Collins 

University of Washington 
Affiliated Hospitals, Seattle 



Elizabeth Schoefer 

Sutter Medical Center, Santa 
Rosa, CA 

GENERAL SURGERY 

Keith Aldrich 

Massachusetts General Hospital 

Nicholas Andersen 

Duke University Medical Center, 
Durham, NC 

Hugh Auchincloss 

Massachusetts General Hospital 

Eric Feins 

Massachusetts General Hospital 

Emily Keung 

Brigham and Women's Hospital 

Teresa Kim 

Massachusetts General Hospital 

Carlos Paz 

University of California- 
Son Francisco 

Babafemi Pratt 

Barnes-Jewish Hospital, St. Louis 

Kristy Rialon 

Duke University Medical Center, 
Durham, NC 

Gary S>vain 

Mount Sinai Hospital, NY 



Marissa Wagner 

Brigham and Women's Hospital 

Yifan Yang 

University of California-Davis 
Medical Center, Sacramento 

INTERNAL MEDICINE 

Aaron Aguirre 

Brigham and Women's Hospital 

Melissa Burroughs 

University of Californio- 
San Francisco 

Jonathan Clarke 

New York Presbyterian Hospital- 
Weill Cornell Medical Center 

Steven Corsello 

Massachusetts General Hospital 

James Davis 

New England Medical Center 

Paul Dieffenbach 

Yale-New Haven Hospital 

Anna Forago 

Brigham and Women's Hospital 

Daniel Freedberg 

New York Presbyterian 
Hospital-Columbia 

Justin Gainor 

Massachusetts General Hospital 

Karimi Gituma 

University of California- 
San Francisco 

Lauren Gold 

Johns Hopkins Hospital 

John Greenland 

Beth Israel Deaconess 
Medical Center 

Nicholas Houstis 

Brigham and Women's Hospital 

Ngozi Iroezi 

UCLA Medical Center 

Jonathan Jacobs 

Stanford University Programs 
Neha Jodejo 

Brigham and Women's Hospital 

Sochin Jain 

Brigham and Women's Hospital 

Cindy Kanegai 

Stanford University Programs 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Joseph Ladapo 

Beth Israel Deaconess 
Medical Center 

Lakshmi Lattimer 

Johns Hopkins Hospital 

Yehoshua Levine 

Massachusetts General Hospital 

Jane Lo>ve 

Brigham and Women's Hospital 

Matthew McCarthy 

New York Presbyterian 
Hospital-Columbia 

Sonali Mukherjee Shah 

Beth Israel Deaconess 
Medical Center 

Meagan Murphy 

Massachusetts General Hospital 

Babak Nazer 

Brigham and Women's Hospital 

Ramon Partida 

Brigham and Women's Hospital 

Parin Patel 

Hospital of the University of 
Pennsylvania, Philadelphia 

Krishna Reddy 

Massachusetts General Hospital 

Mohammed Saeed 

University of Michigan Hospitals, 
Ann Arbor 

Jason Sanders 

Massachusetts General Hospital 

Pritha Sen 

Massachusetts General Hospital 

Kelly Slack 

Massachusetts General Hospital 

Yee-Ping Sun 

Brigham and Women's Hospital 

Anthony Sung 

Johns Hopkins Hospital 

Jonathan Waks 

Brigham and Women's Hospital 

Jaime Wilson-Chiru 

Stanford University Programs 

INTERNAL MEDICINE/ 
PRIMARY CARE 

Allison Ackerman 

Massachusetts General Hospital 

Anna Chodos 

University of California- 
Son Francisco 



Denise De Las Nueces 

Brigham and Women's Hospital 

Rose Kakoza 

Brigham and Women's Hospital 

Brittany Lee 

Massachusetts General Hospital 

Anya Lepp 

Brigham and Women's Hospital 

Stacy Truta 

Brigham and Women's Hospital 

Jennie Wei 

University of California- 
Son Francisco 

MEDICAL ENGINEERING/ 
MEDICAL PHYSICS 

Sharon Fox 

MIT-Harvard Combined Program 

NEUROLOGY 

Amor Dhand 

University of California- 
San Francisco 

Raquel Gardner 

University of California- 
San Francisco 

Paul George 

Stanford University Programs 

Ruchira Jha 

Massachusetts General Hospital 

Sarah Kempe-Mehl 

University of California- 
Son Francisco 

NEUROSURGERY 

Patrick Codd 

Harvard/Massachusetts General 
Hospital 

OB/GYN 

Taniqua Alexander 

University of Virginia, 
Charlottesville 

Morisa Gonzalez 

University of Arizona Affiliated 
Hospitals, Tucson 

Noana Jumah 

University of Toronto 

Tiffany McNair 

Johns Hopkins Hospital 



James Rapley 

Naval Medical Center, 
Portsmouth, VA 

Rachel Weinerman 

NYU School of Medicine 

OPHTHALMOLOGY 

Fatima Ahmad 

Wills Eye Institute, Philadelphia 

Meenakashi Gupta 

Massachusetts Eye & Ear Infirmary 

Nancy Huynh 

Massachusetts Eye & Ear Infirmary 

Yao Liu 

Massachusetts Eye & Ear Infirmary 

Jesse Maki 

University of Southern California, 
Los Angeles 

Glenn Yiu 

Massachusetts Eye & Ear Infirmary 

ORAL AND MAXILLOFACIAL 
SURGERY 

Paul Gordon 

Massachusetts Eye & Ear Infirmary 

Cory Resnick 

Massachusetts Eye & Ear Infirmary 

William Williams 

Massachusetts Eye & Ear Infirmary 

ORTHOPEDIC SURGERY 

Christopher Allmon 

University of Maryland Medical 
Center, Baltimore 



Christopher Bayne 

Rush University Medical Center, 
Chicago 

Micah Berry 

University of Southern California, 
Los Angeles 

Julian Carlo 

University of Iowa Hospitals and 
Clinics, Iowa City 

Collin May 

Massachusetts General Hospital 

Mark Miller 

University of Washington 
Affiliated Hospitals, Seattle 

Miguel Ramirez 

Union Memorial Hospital, 
Baltimore 

Navid Redjal 

Massachusetts General Hospital 

Pedro Roque 

Albany Medical Center Hospital, 
Albany NY 

Anna Stevens 

University of Pittsburgh Medical 
Center 

Bryce Wolf 

Massachusetts General Hospital 

OTOLARYNGOLOGY 

Sunshine D>vojak 

Massachusetts Eye & Ear Infirmary 

Agnieszka Jonisiev^icz 

Stanford University Programs 

Sang Kim 

Massachusetts Eye & Ear Infirmary 




AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



ptjt.se 



MAKING THE ROUNDS AT HMS 



PATHOLOGY 

Siraj Ali 

Beth Israel Deaconess 
Medical Center 

John Dekker 

Massachusetts General hlospital 

Robert Ohgomi 

Stanford University Programs 

Ellen Yeh 

Stanford University Programs 

PEDIATRICS 

Megan Brov\^ning 

University of California, San 
Diego Medical Center 

Melissa Coleman 

Children's Hospital, Los Angeles 

Genevieve Daftary 

Massachusetts General Hospital 

Nina Han 

McGaw Medical Center of 
Northwestern University, Chicago 

Mark Hanudel 

UCLA Medical Center 

Lauren Henderson 

Children's Hospital Boston 

Daniel Horton 

Children's Hospital Philadelphia 

Junne Kamihara 

Children's Hospital Boston 

Kevin Kuo 

Stanford University Programs 

Mollie Lebo>vitz 

Children's Hospital Boston 

Michele Levin 

New York Presbyterian 
Hospital-Columbia 

Jennifer Lewey 

Brighom and Women's Hospital 

Celeste Lopez 

Massachusetts General Hospital 

Leslie McCall 

Children's Hospital Boston 

Christina Mills 

Children's Hospital Boston 

Katherine Nelson 

Children's Hospital Philadelphia 

Kathleen Oldreod 

Oregon Health & Science 
University, Portland 



Raquel Reyes 

Massachusetts General Hospital 

Alyssa Rosen 

Children's Hospital Philadelphia 

Nicole Salozaar-Austin 

Children's Hospital Philadelphia 

Kevin Shapiro 

Children's Hospital Boston 

Siobhan Wescott 

University of New Mexico School 
of Medicine, Albuquerque 

PEDIATRICS/ 
PRIMARY CARE 

Hiu-fai Fong 

Children's Hospital Boston 

PHYSICAL MEDICINE/ 
REHABILITATION 

Gloria Hou 

McGaw Medical Center of 
Northwestern University, Chicago 

PLASTIC SURGERY 

Frank Fang 

University of Michigan Hospitals, 
Ann Arbor 

Thomas Imahiyerobo 

New York Presbyterian 
Hospital-Columbia 

Richard Reish 

Brigham and Women's Hospital 

Jason Souza 

McGow Medical Center of 
Northwestern University, Chicago 

Arthur Turko 

Brigham and Women's Hospital 

PSYCHIATRY 

Percy Ballard 

Cambridge Health Alliance, 
Cambridge, MA 

Claire Brickell 

Massachusetts General Hospital 

Hannah Brov/n 

Massachusetts General Hospital 

Kelly Edv/ards 

Massachusetts General Hospital 



CONNECT THE DOCS 



Harvard Launches the Catalyst Website 

Harvard Catalyst, a University-wide initiative aimed at 
improving human health, was rolled out this year. The 
enterprise seeks to engage faculty and students at 
Harvard's ten schools and eighteen academic health care 
centers. To assist that effort. Harvard Catalyst recently 
unveiled its new website. The site allows investigators to 
form cross-institutional teams, gain access to tools and 
technologies, and obtain seed funding for projects. 
Harvard Catalyst is funded by a five-year, $1 17.5-million 
Clinical and Translational Science Award from the 
National Institutes of Health and an additional $75 mil- 
lion from HMS, other Harvard schools, and affiliated hos- 
pitals. To learn more, visit http://catalyst.harvard.edu. ■ 



Mia Everett 

Hospital of the University of 
Pennsylvania, Philadelphia 

Carl Fleisher 

UCLA Semel Institute for 
Neuroscience & Human Behavior 

Felipe Jain 

UCLA Semel Institute for 
Neuroscience & Human Behavior 

RADIATION ONCOLOGY 

Savita Dandapani 

University of Southern California, 
Los Angeles 

Monica Krishnan 

Brigham and Women's Hospital 

Jonathan Schoenfeld 

Brigham and Women's Hospital 

Monica Sircar 

Memorial Sloan-Kettering, NY 

Cullen Taniguchi 

Stanford University Programs 

RADIOLOGY 

iris Bonilla-Yoon 

UCLA Medical Center 

Amsalu Dabelo 

Yale-New Haven Hospital 

Nathan Himes 

Brigham and Women's Hospital 



Debbie Lee 

Massachusetts General Hospital 

Ruth Magera 

Hershey Medical Center/Pennsyl- 
vania State University, Hershey 

Theodore Marentis 

University of Michigan Hospitals, 
Ann Arbor 

Kathleen Ruchalski 

UCLA Medical Center 

Leo Tsai 

Beth Israel Deaconess 
Medical Center 

Evan Zucker 

New England Medical Center 

UROLOGY 

Christopher Adams 

University of Iowa Hospitals and 
Clinics, Iowa City 

Zorine Balsara 

Duke University Medical Center, 
Durham, NC 

OTHER 

Martin Zalesok 

Life Science Specialist, 
L.E.K. Consulting, Boston 

Suzana Zorca 

Research Fellowship, NIH 
Clinical Center, Bethesda, MD 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



PKESTDENT'S REPORTi I 



Life After Harvard 




INCH LEAVING BOSTON FOUR YEARS AGO TO TAKE MY 

current position in Philadelphia, I am often asked 
what life is like after Harvard. In fact, I feel like I 
haven't really left, in part because I maintain a 
faculty appointment at HMS and often return to teach med- 
ical students and residents, and in part because I'm serving 
as president of the Harvard Medical Alumni Association. 

At our Alumni Council meetings, we hear about all aspects 
of the School — from broad strategic priorities down to the 
details of curricular reform and student debt. At the same 
time, we discuss how the Council can best work with the 
School for the benefit of all relevant parties — alumni, stu- 
dents, and the School itseE So I've only partially severed my 
ties, and I treasure the ones that remain intact. 



members in recognizing that developing the platform and 
the infrastructure for such a community — and then encour- 
aging alumni and students to become active participants — 
is more than a one-year project. We believe, however, that 
it's an important priority. 

What is our vision for this virtual community? Ultimately, 
it will allow alumni to connect with each other and with stu- 
dents around areas of common interest, ranging from clinical 
and research interests to volunteer opportunities. Students will 
be able to hnk with alumni who have specific interests or hve in 
particular geographic areas. Students will also have opportuni- 
ties to seek advice, estabhsh mentoring relationships, and find 
alumni wOling to provide housing during travel for residency 
interviews. Ideally, the community would also provide a portal 



Ultimately, the virtual community will allow alumni 
to link with each other and with students around 
areas of common interest, ranging from clinical 
and research interests to volunteer opportunities. 




Still, I don't think anyone who has gone through the 
extraordinary experience of education at HMS ever com- 
pletely loses the connection. Whatever career path we ulti- 
mately choose, we recognize how strongly our professional 
lives have been shaped by our education, our experiences, 
the contacts we made during our time as students, and any 
additional training or relationships we have maintained 
with the School. During our 35th HMS reunion in June, my 
classmates and I reinforced the bonds we had forged 
decades ago, bonds that hadn't really broken despite many 
years and many miles of separation. 

Throughout the past year, William Chin '72 (my prede- 
cessor as president of the Alumni Association), Judy Ann 
Bigby '78 (my successor), and I have discussed ways in 
which the Council could help strengthen the links among 
alumni, between alumni and current students, and between 
alumni and the School. As we know from social networking 
sites such as Facebook, electronic communication through 
the Web provides us with an unprecedented opportunity to 
establish a virtual HMS community that extends far beyond 
campus. Bill, JudyAnn, and I have joined other Council 



for alumni to experience some of the current curriculum, per- 
haps through access to digitized lectures or other educational 
resources. We are in the early stages of exploring the potential 
applications of such a community, and a range of unanticipated 
appHcations will undoubtedly emerge as alumni and students 
recognize the promise and power of this new community. 

Our priorities now are to develop the infrastructure for 
the virtual community and to establish a robust database of 
all alumni. We will work with the School to determine how 
such a resource is best developed, housed, and financed 
within the complex organizational structure of Harvard. I 
have discussed this priority with Dean Jeffrey Flier, and he 
shares our interest and excitement. 

So, in returning to the question of whether there is life 
after Harvard, my hope is that the question will become 
moot as we use the power of the Internet to help all alumni 
feel connected to the HMS community for life. ■ 

Steven E. Weinberger 73 is senior vice president for medical education at 
the American College of Physicians in Philadelphia. He can he reached 
at sweinherger@acponline.org. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



rf'/x/lxLjIi riljr 



BOOKS BY OUR ALUMNI 





FORENSIC 
, MENTAL 
HEALTH 
TESTIMONY 






PSYCHIATRIC 
GENETICS 

Apptiaaons In Olnluil Pratttee 




The Spirit of the Place 

by Stephen Bergman 73 (as Samuel 
Shem) (Kent State University Press, 2008) 

This novel from the author of The House of 
God follows an expatriate doctor who 
returns to his small hometown after his 
mother's death. While there, he reunites 
with family, comes to terms with old 
rivals, and reconnects with the town 
doctor who once mentored him. 
Bergman's tale underscores the link 
between the health of individuals and 
their communities and reveals what it 
means to be a healer — and to be healed. 



America America 

by Ethan Canin '92 (Random House, 2008) 



Set in a small town during the Nixon era 
and today, Caniris sixth novel tracks the 
journey of Corey Sifter from yard boy on 
the estate of a powerful local family to 
aide to a presidential candidate. As the 
candidate's campaign gains momentum. 
Sifter finds himself caught in a web of 
events in which loyalty, politics, sex, 
and gratitude conflict with morality, 
love, and truth. 

Practical Approaches to Forensic 
Mental Health Testimony 

by Thomas G. Gutheil '67 and 
Frank M. Dattilio (Lippincott Williams 
e!rMlfeins,2007) 



pare for court appearances as mental 
health experts without losing their per- 
spective, integrity, or sense of humor. 
The book includes excerpts of actual 
direct and cross-examinations, accom- 
panied by suggestions for improved 
responses. 

The Mercy Rule 

by Perri Klass '86 (Houghton Mifflin, 2008) 



What makes a good parent — and who 
should judge that? These are questions 
posed in Klass's novel about Lucy, a fos- 
ter-care survivor dealing with similar 
families in her work as a pediatrician. 
As Lucy tries to balance the struggles of 
her patients with those of her own fam- 
ily, she must judge herself as a parent, 
critique other parents, and deal with the 
echoes of her childhood. 

The Jungle Effect 

A Doctor Discovers the Healthiest Diets from 
Around the World — Why They Work and How 
to Bring Them Home, by Daphne Miller '93 
(HarperCollins, 2008) 



This practical guide provides concrete 
approaches to help professionals pre- 



Miller discusses various "cold spots" 
around the world in which certain chronic 
diseases are uncommon — rates of depres- 
sion are lower in Iceland, for example — 
and she explains how following indige- 
nous diets can help readers regain health 
and wellness. The book includes inspi- 
rational stories from Miller's patients, 
interviews with world-renowned food 
experts, and indigenous recipes. Andrew 
Weil '68 provides the foreword. 



Effective Management of flealth 
and Safety Programs 

A Practical Guide, by Royce Moser, Jr. '61 
(Third Edition, OEM Press, 2008) 



Moser's guide stresses how to design, 
implement, evaluate, and obtain support 
for health and safety programs by exam- 
ining practical management techniques 
and apphcations. The updated text con- 
tains five new chapters on subjects such 
as productivity enhancement, entrepre- 
neurship, and planning health care 
responses to mass casualty situations. 
The author also includes examples of 
lessons learned the hard way to help 
readers avoid similar mistakes. 

Psychiatric Genetics 

Applications in Clinical Practice, edited 
by Jordan W SmoUer '9L Beth Rosen 
Sheidley, and Min T Tsuang (American 
Psychiatric Publishing, 2008) 



Written explicitly for practitioners, 
this book is the first to focus on the 
clinical applications of genetics in psy- 
chiatry. The editors explore issues 
involved in genetic counseling, the 
interpretation of familial and genetic 
information for clinical use, informa- 
tion about the risks associated with 
specific psychiatric disorders, the uses 
of genetics testing, and the risks and 
benefits of medication use during preg- 
nancy. The editors also cover ethical, 
legal, and social implications to help 
illustrate the dilemmas that arise with 
advances in genetics research. 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



REVIEWING THE PRINTED WORD [ 



BOOKMARK 




Spiritual Evolution 

A Scientific Defense of Faith, by George Vaillant '59 
(Broadway Books, 2008) 



ECENTLY, A 44-YEAR-OLD SOMALIAN REFUGEE WAS 

brought to the chnic by his group home staff, led 
through the door by the hand. His psychosis had 
begun in the camps, where he would wander away 
safe zones. Years have passed, his country has 
changed, and he is wandering stih, away from group homes, 
from hospitals, and from his small family. He repeats words ff 
they are gently said to him, but otherwise speaks only to him- 
self. What he saw in Somaha has caused him to lose his mind. 

He was in my mind when I read 
George Vaillant's most recent book. 
Spiritual Evolution: A Scientific Defense of 
Faith. Every psychiatric resident — and 
any humanist — should know about 
Vaillant '59, who has led Harvard's 
Study of Adult Development for the 
past three decades. Based on longitu- 
dinal data of the hves of more than 
700 men, Vaillant has given us the 
concept of higher coping defenses and 
proof that early tragedy need not con- 
script the future. He is a great and 
optimistic thinker. 

Perhaps because he is aging like the 
rest of us, Vafflant's more recent preoccupations have grown 
wings. He remains optimistic, but now he is thinking less 
about men and more about mankind. In Spiritual Evolution, he 
wants to convince the reader that "positive emotions are not 
just nice to have, they are essential to the survival of Homo 
sapiens as a species." He doesn't expect us to take his word. He 
presents two hundred pages of proof from genetic, anthropo- 
logical, and developmental sciences. From every angle, he 
makes a case for the "strong causal association between posi- 
tive emotions and post-crisis resihence." But again I thought, 
with some doubts, of my patient. 

The essential positive emotions Vaillant writes about — 
neither the American Psychiatric Association nor Freud ever 
showed much interest in them — are faith, love, hope, joy, for- 
giveness, compassion, gratitude, and awe. They derive neuro- 
anatomically from deep limbic and more superficial frontal 
systems, which have become linked in man through evolu- 
tion. Unselfish love, for instance, is a limbic product; it 
evolved in the brain over millennia "to facilitate... attach- 
ment, social cohesion and spiritual community." Hope, on the 
other hand, is frontal, and a bit more cerebral — it requires a 
comprehension of time, past and future. 




The positive emotions are parasympathetic; vessels dilate, 
heart rate calms, oxytocin flows. We feel empathic, relaxed, 
and communal-minded. In contrast, negative emotions such 
as fear and anger — which some might argue also are essen- 
tial — cause us to feel cramped and seff-serving. They are 
physiologically catabohc. The woeful restating here is mine — 
Vaillant uses much greater sophistication and intelhgence to 
lay out the details. Still, we all get the point, and, given a 
choice, know which feelings we would put our money on. 

Each emotion receives a chapter, explaining its many 
healthful, fruitful facets. It is as ff the author is rotating cut 
diamonds to view them from all angles. This results in some 
excellent cocktail party facts — for instance, "two table- 
spoons of gray matter were added [to primate brains] every 
100,000 years" — and some lovely poetic notions: "compassion 
is the desire to separate someone, 
even if unappealing, from his suffer- 
ing"; "forgiveness increases steadily 
from age 3 to age 90." 

But being human, VaiUant writes, 
we also struggle against ourselves. 
With the development of language, we 
gained poetry and logic, science and 
measurement, at the expense of spiri- 
tuality or proper regard for these essen- 
tial feehngs. Science itself has had htde 
interest in studying them. And tradi- 
tional fundamentalist religions have 
excluded "the amalgam of positive 
emotions that bind us to other human 
beings." Instead, these religions are mostly "dry cognitive 
questions about patriarchal gods and 'me,' " not the inclusive 
social communities that will save us. 

Any encompassing theory of humanity has to make room 
for evil. In his book, Vaillant addresses it with brevity, as a 
force whose time has more or less come and gone. He points 
out that the Nazis "lasted barely a decade, but after 1,500 years 
the Benedictine Order is still ahve and well." This may be true, 
but it made no difference to the victims, or to my own devas- 
tated and wandering patient. Natural selection, cultural 
anthropology, and moral development did nothing for them. 
That is the sadness of theories. They cannot fit us all. 

Vaillant writes with such charisma and personal passion, 
such optimism after so many decades in the people business, 
that sometimes Spiritual Evolution teeters on the precipice of 
seff-help. But then he catches himseff. "As soon as my writing 
becomes prescriptive," he admits, "as soon as I suggest that I 
know how or why spiritual enlightenment and mystical expe- 
riences develop, I have lost my way." 

Ah, I thought with relief, that is the conclusion of a wise man. ■ 

Elissa Ely '88 is a psychiatrist at the Massachusetts Mental Health Center 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 




RENCHMARKS 



DISCOVERY AT HMS 



Double Trouble 




LTHOUGH MUCH HAS BEEN 

learned since Alois Alzheimer 
first identified abnormal 
plaques and tangles in the 
brain of a woman with dementia, treat- 
ments for Alzheimer's disease remain 
largely ineffective and diagnostics inade- 
quate. New research from a collaboration 
led by an HMS professor may help address 
these shortcomings. 

Using extracts from human brain tis- 
sue, Dennis Selkoe, the Vincent and Stella 
Coates Professor of Neurologic Diseases 
in the Department of Neurology at 
Brigham and Women's Hospital, and col- 
leagues showed that a two-unit peptide of 
human amyloid-beta protein (A|3) can 
induce the synapse dysfunction and 
loss that are hallmarks of early-stage 
Alzheimer's. This dimer is the smallest 
configuration possible for the protein. The 
study, published in the August issue of 
'Nature Medicine, provides insight into how 
the disease begins in the human brain 
and how it might be treated. 

"All forms of Ap are bad 
news," says Selkoe. "You don't 
want it to build up. But smaller 
assemblies are worse." Such 
assemblies are the first ones to 
form when the body produces 
excess A|3. 

The results are compelling; 
until now, evidence of the pro- 
tein's involvement in Alzheimer's 
came only from model experi- 
mental systems in which synthe- 
sized forms of Ap or Ap produced 
from cell cultures were used. 
"That's fine," says Selkoe. "But 
why don't we go right to 
the source?" 

Source Material 



Shankar extracted material from these 
brains and found substantial amounts of 
soluble Ap in the Alzheimer's brains, but 
httle in the others. 

Soluble Ap oligomers may float freely 
inside the brain's fluid-filled extracellu- 
lar spaces. Over time, these soluble com- 
plexes form insoluble fibrils that are 
deposited as amyloid plaques. The 
research team elected to focus on the 
levels of soluble Ap. Previous research 
had shown these levels correlate most 
strongly with cognitive symptoms in 
Alzheimer's disease. 

The scientists found that soluble Ap 
that was extracted directly from the 
human cortex was a potent inhibitor of 
long-term potentiation, a neural mecha- 
nism important to the formation of new 
memories, in the hippocampus of normal 
mice. Soluble Ap also facilitated long- 
term synaptic depression, essentially 
priming hippocampal neurons to tune 
some signals out. 



Unkind Cuts 

To test the effects of soluble human Ap on 
the synapse, Shankar and Selkoe connect- 
ed with Bernardo Sabatini '95, an HMS 
associate professor of neurobiology. In 
2007, Sabatini and Shankar showed that 
soluble Ap from cultured cells disrupted 
synaptic spines. In this new work, 
Shankar and Sabatini repeated those 
experiments using soluble Ap oUgomers 
from Alzheimer's brains. Again, they 
observed synapse loss. According to 
Sabatini, the human Ap ohgomers appear 
to be activating a normal pathway and 
biasing it toward synapse loss. 

The team then collaborated with 
researchers at the University College 
Dublin to test the human peptide's effect 
on behaxior. The scientists injected the 
brains of rats with either a sample of sol- 
uble human Ap or a sample from which 
the Ap had been removed. Although the 
rats in the experiment had previously 



Selkoe and coauthor Ganesh 
Shankar '10 did just that by 
starting with donated brain 
specimens from deceased patients 
who had some form of dementia. 




10 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 




Regulatory Concerns 



been trained to avoid a dark chamber, 
exposure to the soluble form caused the 
rats to go back into the dark chamber as if 
they had never been trained. 

The group then turned from free-float- 
ing A(3 assembhes to the largely insoluble 
amyloid plaques, also extracted from the 
brains of humans with Alzheimer's dis- 
ease. The researchers found some good 
news: Isolated plaques generally did not 
exhibit biological activity on synapses. 
Instead, they seemed to act as reservoirs 
that collect and sequester smaller amyloid 
assemblies, thereby keeping toxic A(3 
ohgomers out of circulation. This suggests 
that plaques, though they may have some 
pathologic effects, are not principally 
involved in initiating early synaptic 
impairments in Alzheimer's disease. 

Selkoe believes, however, that plaques 
have a maximum capacity. Once that 
capacity is reached, he says, excess free- 
floating assemblies, including toxic solu- 
ble dimers, have nowhere to go and so are 
free to diffuse into synaptic clefts and 
cause injury. 

Shankar and Selkoe also undertook 
experiments to chemically isolate A(3 
isoforms from the human brains used in 
the study. They found A|3 exists in many 
different-sized forms. In addition, they 
found the soluble human A(3 dimer 
inhibited long-term potentiation while 
monomers and other higher- order 
assemblies did not affect this form of 
synaptic plasticity. 

Shankar has tested several potentially 
therapeutic A(3 antibodies and found that 
targeting duners may be effective, with 
those directed to the peptide's N-termi- 
nus most effective at neutralizing the 
dimers' adverse effects. Unpublished 
results of a trial of a humanized version of 
the same antibody reported by other 
researchers also showed positive clinical 
benefits in certain Alzheimer's patients in 
the mild to moderate stages of disease. ■ 

Elizabeth Dougherty is a science writer for 
Focus. 



THE THYROID GLAND CAN BE 

a capricious organ, spilling out 
too much or too little of its vital 
hormones. An excess or lack 
can lead to a panoply of debil- 
itating mental conditions. 
Indeed, physicians will typical- 
ly check thyroid hormone lev- 
els in patients complaining of 
memory loss or depression. It 
now appears they may have 
another reason to check thy- 
roid function in their female 
patients. A new study suggests 
that women with low or high 
levels of thyroid-stimulating 
hormone (TSH) are more likely 
to develop Alzheimer's disease 
than those with normal levels. 

A team of researchers fol- 
lowed 1,864 participants in 
the Framingham Heart Study 
whose thyroid function — and 
TShI levels — had been mea- 
sured between 1977 and 
1979. Zaidy Tan, an HMS 
assistant professor of medicine 
at Beth Israel Deaconess Med- 
ical Center, together with col- 
leagues at HMS and Boston 
University, monitored the partic- 
ipants for an average of 12.7 
years and found that women 
with TSH values in the lowest 
and highest third — less than 1 milli-international unit per liter or more than 2.1 milli- 
international units per liter — ^were twice as likely to develop Alzheimer's disease as 
those with values in the middle third. Men were not at similar risk. 

The researchers, who published their findings in the July 28 issue of Archives of 
Internal Medicine, found an elevated risk even in women who, at some point, had 
undergone hormone supplementation or suppression therapy, suggesting the effects 
of low and high TSH levels may be irreversible. 

The finding that puzzles the researchers is that only women were vulnerable to the 
effects of aberrant hormone production. In fact, women appear to be more vulnera- 
ble to other thyroid-associated conditions, such as Graves' disease. 

As to how this dysregulation links to Alzheimer's disease, the investigators pose 
an intriguing hypothesis. According to Tan, too little or too much thyroid hormone 
could lead to irregularities in the regulation of the amyloid precursor protein gene, 
which is controlled by TSH and known to play a role in Alzheimer's. Abnormal levels 
may cause aberrant production of plaque-causing amyloid proteins. ■ 

Misia Landau is the senior science writer for Focus. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



11 



*y^ 



^- ^- 



-*vr 




ij: 



m^ 




#: 










Our brains make, hold, and lose memories in response 




AUTUMN 2008 • HARVARD MEDICAL ALUMNJ BULIFm 




WE DO IS IS BASED ON A MEMORY. EACH 
thought, each movement, each conversation draws upon the 
hbrary of Me that is nestled within our brains. From the moment 
of our birth until the moment we die, our brains, with their bil- 
lions of neurons and trillions of neuronal connections, gather, 
package, and store the sensory information transmitted by our 
eyes, ears, nose, and skin so that we may access and apply it to the 
physical, intellectual, and social demands of the world we inhabit. 



Yet, just as our muscles change with age, 
so, too, do our brains. Small wonder, 
then, that explorations into how age- 
related changes aEect our brains — and, by 
extension, the ways we engage with our 
world — have so captivated researchers, 
observers, and those who simply hope to 
keep the old bean keen. 

Down Memoty Lane 

In 1906, the Spanish anatomist Santiago 
Ramon y Cajal received a Nobel prize for 
his "neuron doctrine." Neurons, he said, 
fijnction as discrete units. Each cell body 
receives signals from a rootlike array of 
dendrites and transmits those signals 
along an axon to the waiting dendrites of 
other neurons. Researchers later showed 
that transmissions from axon to den- 
drites occur across synapses and that 
neurotransmitters — substances such as 
dopamine, acetylcholine, and sero- 
tonin — help signals jump these clefts. 

The idea that neurons form networks 
that orchestrate our ability to buUd 
memories was posited in 1949 by Cana- 
dian psychologist Donald Hebb. From 
his studies of how the brain commanded 
behavior, Hebb postulated that when 
one neuron repeatedly caused another 
neuron to fire, a type of metaboHc bond- 
ing occurred. His idea spawned a slogan; 
Neurons that fire together wire together. 
This fire-vdre partnership, researchers 
later discovered, results in networks of 



connected neurons, each a memory trace 
of a learned experience that expands or 
modifies other traces. 

When functioning efficiently, the more 
than 100 biUion neurons in the adult 
brain provide access to a phenomenal 
cache of information. Researchers have 
found that it is the degree to which our 
aging, changing brains construct new 
connections between these neurons — 
and avoid or minimize the destruction of 
existing ones — that determines the scope 
and vitahty of these networks. 

"The aging process does not appear to 
be a passive one," says Bruce Yankner, a 
professor of pathology and neurology at 
the Paul F. Glenn Laboratories for the 
Molecular Biology of Aging at HMS. "It 
instead appears to be a balance between 
stress and compensation." 

One of the leading theories for how the 
brain confronts age-related changes is the 
concept of synaptic plasticity. This theo- 
ry holds that our brains continually 
remodel themselves, tweaking the num- 
ber of connections to other neurons so as 
to embrace new information, eliminate 
links to unused networks, and reflect 
new complexities associated with infor- 
mation in other traces. 

"Synaptic plasticity truly is an excit- 
ing concept because it says the brain is 
not a fixed structure," says Majid Fotuhi 
'97, an assistant professor of neurology at 
the Johns Hopkins University School of 
Medicine and director of the Center for 



14 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Memory and Brain Health at Sinai Hos- 
pital's LifeBridge Health Brain & Spine 
Institute. "One cell may have a thousand 
synapses on it but then something hap- 
pens — ^you learn something new — and 
you might then have a thousand and 
twenty synapses." 

Situations that trigger these types of 
changes occur constantly. Negotiating a 
reduction of global carbon dioxide emis- 
sions, for example, could trigger synaptic 
growth. So could preparing dirmer. 

Let's say you use a particular pot regu- 
larly. You know it has a small break in the 
handle, but it's usable, so you puU it out, 
fiU it with soup, and place it on the stove. 
After the soup heats, you reach over to 
pull the pot off the burner. You get 
burned. A strong signal associated with 
the pain speeds to your brain, as does 
the realization that you have touched 
exposed metal in the handle. Your brain 
uses this information to establish new 
connections; you learn to avoid using 
that pot or to use a potholder when han- 
dling it. You have estabUshed a memory 
that, like most memories, helps you func- 
tion better in your world. 

Form and Function 



Viewed without its protective bony outer 
structure or the rugged inner membrane 
that wraps its mass of cells, the brain's 
cortex bears an uncanny resemblance to a 
shelled walnut. This wrinkled, bisected 
structure is arguably the most sophisti- 
cated area of the brain. 

Within each cortical hemisphere is 
tucked a small structure quite active in 
memory making: the hippocampus. 
Shaped like a banana, the hippocampus 
serves as an active way station for infor- 
mation, holding new material that is 
needed immediately, sending to storage 
that which will be held for days or 
decades, and assisting in the recall of 
data housed in other cortical areas. 

The cortex is involved primarily in 
declarative memory, which captures the 
facts and events of our lives and allows 
for their recall in some tangible manner: 



the spoken word, a visual representation, 
a gesture. Declarative memory can be 
held for a short time, as for a one-time 
use of a telephone number, or it can be 
held up to a lifetime. And although 
synaptic plasticity can help keep it 
robust, biology and environment do con- 
spire to whittle away at it over time. 

A second form of memory, procedural 
memory, primarily engages noncortical 
areas of the brain, most notably the cere- 
bellum. Procedural memory involves 
sequential, coordinated movements, 
such as those associated with riding a 
bicycle. Unlike declarative memory, pro- 
cedural memory is rugged and not easily 
lost to the passage of time. This form 
of memory is a product of action, an 
imprint of repetitive, serial movements 
that can be acquired only through phys- 
ical participation. 

Adjusting the Volume 

Age-related changes to our brains influ- 
ence the speed with which we can 
access stored information, the complex- 
ity of the neural networks that con- 



tribute to those memories, and the level 
of function of certain cortical areas. 

The fetal brain produces cells and con- 
nections in quantities that far exceed the 
numbers that will populate the adult 
brain. As newborns soak up information 
critical to functioning within their envi- 
rormient, competitive elimination starts 
to prune away unused or underused 
cells. Initially, the neurons and synaptic 
connections, known collectively as gray 
matter, are focused on taking in informa- 
tion and learning. By six months, howev- 
er, researchers have found evidence of 
declarative memory as infants are able 
to recall one or more steps in a simple 
sequence of events within 24 hours of 
having learned them. 

In another three months, infants can 
recall isolated steps from a sequenced 
action after as many as five weeks. By 14 
months, babies can recall several steps of 
a multi-step action for as long as four 
months while 20-month-olds can recall 
all the steps — and their proper order — 
after six months. 

The robust nature of this progression 
in behavior mirrors a flurry of develop- 




AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 




The brairis cortex bears an uncanny 
resemblance to a shelled walnut. This 
wrinkled, bisected structure is arguably 
the most sophisticated area of the brain. 



ment wdthin the structures of the fetal 
and infant brain. The cells that make up 
much of the hippocampus form in the 
first 17 weeks of fetal development and 
have ordered themselves in the loca- 
tions they will hold in the adult brain 
well before birth. Hippocampal synaps- 
es also develop quickly; they are present 
in the fetus by 15 weeks, ramp up their 
numbers after birth, and reach adult 
levels by approximately six months. 

Certain subdivisions of the hip- 
pocampus are slower to develop. An 
area known as the dentate gyrus, 
important in consolidating new infor- 
mation, has about 70 percent of its adult 
complement of cells at birth and 
achieves full adult morphology after 12 
months. Synaptic development in this 
subregion also lags that for the hip- 
pocampus: Between 8 and 12 months, 
the number and density of its synapses 
spike to a level above that supported 
during adulthood. By age five, selective 
pruning has decreased the number of 
connections to that found in adults. 

Development in other association areas 
of the cortex mirrors that of the dentate 
gyrus. Cortical definition begins around 
28 weeks of gestation, with synaptic 
densities in areas critical to association 
and storage peaking in infants by age 
two. Around the same time, the number 
of synapses in the prefrontal cortex tops 
out. In the mature brain, this cortical 
region provides temporary mental work- 
space, known as working memory, for 
processing decisions that involve com- 
plex behavior and problem solving. 

Overall, the number and density of 
synapses most capable of plasticity 
increase throughout childhood. By age 
four, however, increases of this gray mat- 
ter are outpaced by growth in the volume 
of white matter, the mass of networked 
neurons whose axons are wrapped in 
insulating myelin. Myelinated axons 
propel information up to a hundred 
times more quickly than their gray mat- 



ter counterparts, allowing for quicker 
access and recall of information. In the 
brain, the period during which its vari- 
ous regions are most actively pruning, 
myelinating, and maturing — a period of 
neural growing pains, as it were — coin- 
cides with another period known for its 
awkwardness: adolescence. 

Gear Up 

"The cortex of a young person," says 
Zaldy Tan, an assistant professor of med- 
icine at HMS and director of the Memo- 
ry Disorders Clinic at Beth Israel Dea- 
coness Medical Center, "looks like a 
comphcated mass of wrinkled fat tissue, 
with numerous peaks flanked by valleys. 
But as the brain ages, its appearance 
smoothes out; the peaks flatten and the 
valleys widen." These topographic alter- 
ations are the result of changes to the 
brain's volume and cellular material. 

The ratio of gray matter to white mat- 
ter begins to shift from age four through 
early adulthood. Although the precise 
reason for this has not been found, neuro- 
scientists speculate it may be twofold: an 
increase in mature, myelinated regions 
plus the pruning of less productive gray 
matter synapses. Researchers even have 
movie-like evidence supporting this 
conjecture. In time-lapse sequences of 
gray matter-to-white matter changes, 
researchers found that the cortical 
regions in adolescents mature in an order 
that echoes behavioral progression. First 
the primary sensorimotor areas along the 
frontal-to-occipital axis myelinate, then 
back-to-front myelination occurs from 
the parietal lobes to the frontal lobes. 

The prefrontal cortex, that working 
memory reservoir useful in decision- 
making, is among the last to mature. Part 
of that maturation involves an increase in 
the role of dopamine, a neurotransmitter 
critical to deciphering enviroimiental 
cues when choosing between conflicting 
options. Inputs for this chemical increase 



significantly during adolescence. Expo- 
sure to dopamine is thought to con- 
tribute to the development of our abihty 
to use ideas to achieve a goal rather than 
simply acting instinctively in a given sit- 
uation. In broad strokes this means an 
adolescent's reflexes and keeimess of 
sight and hearing are honed well before 
the young person's abihty to process 
complex information is. 

Even synaptic pruning, which begins 
in earnest in childhood, changes focus 
during adolescence. Pruning in the early 
brain targets low-performing excitatory 
synapses that transmit information 
neuron to neuron, a reasonable approach 
considering the efficiency with which 
children and early adolescents need to 
learn. But by late adolescence, pruning 
zeroes in on inhibitory synapses, which 
control the flow of information between 
neurons. Thus, the developing brain 
grows in its abihty to control not only 
the speed by which signals travel but also 
the efficiency of their routes. The result: 
actions grow nuanced so as to, in a sense, 
reflect a synthesis of information leav- 
ened by learning and experience. 

All this upheaval calms by age 30, 
when the number of cell-to-cell contacts 
achieves an adult pattern and the num- 
ber of neuronal connections reaches a 
near steady state — except among adults 
who prod their brains to do more. 

New Tricks 



Normal aging in the brain can mean htde 
notable behaxioral change for an adult 
untroubled by trauma to the head, dis- 
ease that affects the brain, or excessive 
stresses, whether from responsibihty, 
diet, or Mestyle. Physiological changes do 
occur — synaptic connections lessen, the 
volume of certain cortical areas diminish- 
es, and the production of neurotransmit- 
ters decreases. Yet the adult brain may 
actually be able to compensate for these 
alterations: Some research indicates cor- 



16 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



tical regions team up to accomplish work 
previously done individually. 

Researchers looking at cross-sectional 
behavioral data for individuals between 
the ages of 20 and 80 have found httle to 
no evidence for accelerated declines in 
the latter decades for such capacities as 
processing speed, working memory and 
the encoding of new declarative memo- 
ries. There is evidence, however, for lin- 
ear declines in these areas — as well as in 
spatial abihty and reasoning — beginning 
by age 40 or 50. In one area, speed of pro- 
cessing, several studies have found a 
2 percent decline per decade after age 30. 

"The decrease in speed of mental 
processing that is seen with age is not 
a problem," says Tan. "The brain may 
become less efficient, but that doesn't 
mean it also experiences a decrease in 
absolute memory." 

To tease out secrets to healthy brain 
aging. Tan is mining a 60-year data trove 
on the health of another organ; the heart. 

"Study upon study has shown that 
physical activity actually decreases one's 
risk of cognitive dechne with age," Tan 
says. "But what has really struck me 
from my work with the Framingham 
Heart Study is that healthy aging seems 
to mean that what's good for the heart — 
a healthful diet, exercise, low choles- 
terol — is good for the brain, too." 

The boost that cognitive health can 
get from good cardiac health can be 
augmented by good social health, accord- 
ing to Robert Waldinger '78, an HMS 
associate professor of psychiatry and 
director of The Study of Adult Develop- 
ment at Brigham and Women's Hospital. 

"There is strong evidence that peo- 
ple who are more connected to others, 
whether through marriage, friendships, 
children, or grandchildren, do better 
physically, cognitively, and emotionally," 
Waldinger says. "Loneliness, in fact, is 
considered a risk factor for aging poorly." 

But with a finely tuned organ such as 
the brain, httle things can mean a lot. 



Take genes, whose business it is to over- 
see our molecular world. Several years 
ago Yankner looked at the genetic signa- 
tures of the brains of people whose ages 
ranged from 26 to 106. He found that cer- 
tain genes control the formation of new 
synaptic connections, others respond to 
age-induced stresses such as the DNA- 
damaging molecules known as free radi- 
cals, and still others are especially vul- 
nerable to DNA damage. An intriguing 
possibihty is that these genetic charac- 
teristics may predict the brain's future. 

"We found that gene expression was 
quite similar among young adults under 
40 and somewhat similar among adults 
over 70," Yankner says. "But those between 
40 and 70 showed a good deal of variabil- 
ity — some looked like the young group, 
some like the older group. This told us 
that the aging process that determines 
how you're going to fare at age 80 proba- 
bly begins around age 40 or 50." 

Reserving Space 

Barring trauma or illness that would 
affect brain health, the ability of neu- 
rons to ramify remains strong through- 
out a person's life. One of the more cap- 
tivating ongoing investigations of brain 
health began nearly 20 years ago with a 
pilot study that looked at healthy aging 
in residents of a retirement community 
of Catholic nuns. This largely closed 
community provided the researchers 
with a nearly ideal set of participants; 
the nuns had not only carefully pre- 
served their personal and medical histo- 
ries but they had also conformed to a 
documented lifestyle. In addition, the 
nuns agreed that, after their deaths, their 
brains would be donated to the study. 

The investigators explored these pre- 
cious donations in the hopes of isolating 
factors that affected the nuns' cognitive 
functioning. They found that cognitive 
capacity was compromised for women 
whose brains showed signs of cardiovas- 



cular disease, such as brain stroke. But 
they found cognitive function remained 
strong for women whose brains showed 
little to no evidence of cardiovascular 
trauma. Perhaps most interestingly, the 
researchers also found strong cognitive 
functioning among stroke-free women 
whose brains showed moderate to 
advanced Alzheimer's disease. Such 
brains, they speculated, drew upon 
reserves that delayed or offset the symp- 
toms of dementia. 

Cognitive reserve — the capacity to 
sustain brain function and to build effec- 
tive networks that are less susceptible to 
disruption, including that which accom- 
panies normal aging or even disease — is 
a growing concept among neuroscien- 
tists. While not exactly a 401(k) for your 
brain, cognitive reserve acquired from a 
life of active and sustained learning can 
keep the brain healthier, longer. 

"Cognitive reserve is like strength 
training for your muscles," Fotuhi says. 
"When you are fit, you can sustain that 
fitness for a long period of time. There is 
compelling evidence that synaptic plas- 
ticity continues through age 70 and that 
brain volume can even increase among 
healthy adults, especially those who 
enjoy teasing their brains and exercising 
regularly. The idea that plasticity exists 
only ui children is completely outdated." 

Research on the molecular and phys- 
ical changes that the brain undergoes 
with time wiU likely continue to over- 
turn contemporary ideas of how age, 
disease, and lifestyle affect our ability to 
gain, maintain, and recall our individual 
library of memories. That our brains do 
alter with age is undeniable. But the lens 
of research increasingly shows us that 
when good overall health is maintained 
and brains are kept agile through learn- 
ing and challenge, life — and memory — 
can remain rich for a long time. ■ 

Ann Marie Menting is associate editor of the 
Harvard Medical Alumni Bulletin. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



17 



t ./ 



m > W'^. 



# 



itfw 



.« If ^i 




t 




,4S 



# 




WHAT TANGLED 




People with 

Alzheimer's disease 

tend to weave 

modifications 

into their 

memories. 

hy Andrew E. Hudson 



"Of course I pay my bills each month/" my patient 
said, as the daughter sitting next to him shook her head. Later, while 
he was undergoing cognitive testing, she explained more fully: 
"That's the problem — he remembers doing things he hasn't done. 
When the electric company shut off his power, we found he hadn't 
paid any bills for about six months. He swears he paid them all. I 
worry whether he can keep living alone. He tells me he takes all his 
medications, but how do I know that's true?" 

People with Alzheimer's disease not only fail to remember previ- 
ously learned information, but they also experience distortions of 
memory and false memories. Distortions of memory may include sim- 
ple but critical aspects of daily life. Alzheimer's patients may falsely 
remember, for example, that they have already turned off the stove or 
taken their medications, leading them to neglect these tasks. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



19 




method of creating false memories is to present 
a list of words — such as candy, sour, sugar, hitter, 
taste, honey, heart, and cake — that all relate to a 
theme word, which is not itself presented. 



More dramatic distortions of memory 
occur when Alzheimer's patients substi- 
tute one person in a memory for another, 
combine two memories, or beheve that a 
long-ago event occurred recently. These 
distortions may fall under the definition 
of confabulation — ^when people fill a gap 
in their memory with a fabrication they 
beheve to be true. 

Sometimes a false memory can be 
confused with a psychotic delusion or 
hallucination. A person may claim, for 
instance, to have recently seen and spo- 
ken with a long-deceased family mem- 
ber. Although visual hallucinations are 
part of Parkinson's disease dementia and 
dementia with Lewy bodies (dementias 
that are characterized by parkinsonism, 
visual hallucinations, ,and fluctuations), 
an Alzheimer's patient is usually more 
likely to suffer from a memory distortion 
or a false memory than a true auditory 
and visual hallucination. The same is 
true for patients who claim that some- 
one has broken into their house and 
rearranged their belongings. That these 
symptoms likely represent false memo- 
ries rather than true hallucinations or 
delusions has treatment implications, 
as false memories respond better to 
memory-improving medications than 
to antipsychotics. 

My interest in memory distortions 
began with a simple clinical observation: 
most of my patients with memory prob- 
lems triggered by mild Alzheimer's dis- 
ease could not hve alone, while most of 
my patients with memory problems 
stemming from encephalitis, temporal 
lobe epilepsy surgery, and other etiolo- 
gies could live independently. It was 
clear that something other than simple 
memory loss was at work in those 
with Alzheimer's. My discussions with 
patients and their caregivers soon 
showed that false memories and memory 
distortions made the use of routines and 
reminders more difficult for Alzheimer's 
patients than for those with memory loss 
from other conditions. 



Bearing False Witness 

At Bedford Veterans Administration 
Hospital in Massachusetts, my col- 
leagues and I began our research into 
memory distortions by creating false and 
distorted memories in healthy older 
adults and then determining whether 
Alzheimer's patients could use the same 
mechanisms that the healthy partici- 
pants used to suppress these false mem- 
ories. We created false memories by pre- 
senting healthy people with a list of 
words — such as candy, sour, sugar, hitter, 
taste, honey, heart, and cake — that related 
to a theme word, which was not itself 
presented. Study participants were 
highly likely to falsely remember on 
free-recall tests and falsely recognize 
on recognition memory tests the theme 
word — in this case, sweet. (Even healthy 
younger and older adults falsely recog- 
nize more than two-thirds of such 
theme words.) 

One way to reduce false recognition in 
healthy individuals was simply to have 
them repeat the theme word several 
times. These repetitions helped them 
recall particular words, thus allowing 
them to resist the lure of the non-present- 
ed yet central theme word. In two stud- 
ies, we found that repetition allowed 
healthy older adults to develop specific 
recollection of words on the hst, which in 
turn reduced their rate of false recogni- 
tion. Among Alzheimer's patients, how- 
ever, repetition only helped them grasp 
the theme of the hst, thus leading them 
to err more often in choosing the theme 
word, paradoxically increasing their false 
recognition rate. 

Another way that healthy individuals 
reduced false recognition of related 
words was by pairing the words with 
pictures. Although this reduction could 
simply reflect the fact that pictures 
are better remembered than words, 
researchers at Harvard University have 
shown that false recognition decreases 
because the stories that form from pic- 



ture-word pairings are more distinctive, 
and thus, more memorable. 

The basic idea of this heuristic is that 
some events are so distinctive they 
would have to be memorable. If you were 
asked, "Have you killed a fly in your 
office within the past year?" you might 
find the answer elusive, because for most 
people killing a fly is neither remarkable 
nor distinctive. If instead the question 
was "Have you killed a snake in your 
office within the past year?" you would 
answer confidently, because the memory 
would have been distinct. 

We investigated whether Alzheimer's 
patients could use this distinctiveness 
heuristic to reduce their false recogni- 
tion rates. We experimentally deter- 
mined that Alzheimer's patients could 
use the heuristic. Their poor memory, 
though, limited their ability to reduce 
their false recognition rate. 

In Living Memory 

Studying the frequency of memory dis- 
tortions and false memories in the real 
world can be difficult. The terrorist 
attacks of September II, 2001, though, 
provided us an opportunity. We contact- 
ed Alzheimer's patients and healthy 
older adults with a phone questionnaire 
within weeks of the attacks, again three 
to four months later, and finally one year 
afterward to evaluate both their memory 
of and emotions about that day. 

Memory distortions were common 
among all participants, reminding us that 
a vivid memory isn't necessarily an accu- 
rate memory. Even healthy older adults 
showed a high rate of memory distor- 
tions — on average 25 percent — as they 
misremembered such details as where 
they were and whom they were with 
when they first heard of the attacks. 
Alzheimer's patients showed even less 
accuracy, with memory-distortion rates 
approaching 50 percent. In contrast, 
memory-failure rates — ^with study partic- 
ipants saying, "I don't know" or the equiv- 



20 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 




alent — ^were relatively low: 13 percent in 
the Alzheimer's patient group and only 
1 percent in the healthy older adult group. 
Thus, when it comes to remembering per- 
sonal information related to national trau- 
matizing events, Alzheimer's patients and 
healthy older adults are more likely to 
misremember than to say "I don't know." 
We recently conducted several labora- 
tory studies that also have real-world sig- 
nificance. In one of these studies, we first 
presented Aizheimer's patients and older 
adult controls with sentences that could 
be either true or false, followed by a label 
of true or false. For example, "In New York 
City, the 53rd Street bus will take you 
uptown: /flise," or "It takes 32 coffee beans 
to make a cup of espresso: true." Interest- 
ingly, although the Alzheimer's patients 
correctly remembered that 69 percent of 
the true statements were true, the same 
patients incorrectly remembered that 59 
percent of the false statements were true. 
This finding suggests that if you tell 
someone with mild Alzheimer's disease 
that something is false, they are more 
likely to remember that it's true. The 
statement, "The 53rd Street bus won't 
take you to your sister's house, so take 
the 67th Street bus instead," for exam- 
ple, will lead an Alzheimer's patient to 



be more likely to falsely remember that 
the 53rd Street bus is the correct bus 
than if the 53rd Street bus had not been 
mentioned at all. This finding has sig- 
nificant relevance for clinicians and 
caregivers who need to communicate 
with Alzheimer's patients. 

Brain Storming 

To begin to unravel the underlying 
pathophysiology of these memory distor- 
tions in Alzheimer's patients, we elected 
to test the role that frontal-lobe patholo- 
gy may play in the disease. We began by 
examining false recognition in patients 
with frontal-lobe lesions caused by 
stroke or tumor resection. We gave these 
patients and matched control subjects 
the same related- word Hsts we had given 
Alzheimer's patients and found that 
patients with frontal lesions showed 
even higher levels of false recognition 
than the Alzheimer's patients did. 

Some of our newer research investi- 
gates how the brain forms and retrieves 
memories. In this work, we use 128 chan- 
nels of EEG to produce a particular type 
of neural activity as subjects are shown a 
picture or presented with a previously 
studied word. We found that when we 



average the EEG across 30 or so trials, 
we can see — in real time — the electri- 
cal activity associated with retrieving a 
memory. These studies have shown that, 
compared with healthy older adults, peo- 
ple with mild Alzheimer's disease exhib- 
it vastly reduced frontal-lobe activity, 
thus providing support to the hypothesis 
that frontal-lobe dysfunction may cause 
the high levels of memory distortions in 
people with mild Alzheimer's disease. 

An improved understanding of the 
causes of false memories and memory dis- 
tortions may lead to behavioral and phar- 
macological treatments that can decrease 
their effects. Reducing the effects of 
these tangled memories may in turn 
allow patients with Alzheimer's disease 
to live fuller, more independent lives. ■ 

Andrew E. Budson '92 is director of the Center 
for Translational Cognitive Neuroscience and 
the Geriatric Research Education Clinical Cen- 
ter at Bedford Veterans Administration Hospital 
in Bedford, Massachusetts. He is also director 
of cognitive neuroscience research at the 
Alzheimer's Disease Center at Boston Universi- 
ty School of Medicine and a consultant neurolo- 
gist in the Division of Cognitive and Behavioral 
Neurology at Brigham and Women's Hospital in 
Boston, Massachusetts. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 21 



what happens when memories are too painful to bear? 

hy Jessica Cerretani 




IN THE FILM ETERNAL SUNSHINE OF THE 
Spotless Mind, a man visits a doctor who offers 
him an unusual solution to coping with his 
painful breakup; targeted memory erasure, a 
procedure guaranteed to wipe out all recollec- 
tion of his failed relationship. Fiction, to be 
sure, but research currently taking place at 
Massachusetts General Hospital may someday 
help cement medicine's ability to dull — 
although not completely eliminate — certain 
traumatic memories. 

Forgetfulness isn't usually something we 
welcome. People with post- traumatic stress 
disorder (PTSD), however, can find persistent 
memories of past trauma so overwhelming 
that they have difficulty functioning in the 
present. For these people, says Roger Pitman, 
an HMS professor of psychiatry and director 
of the PTSD Psychophysiology Laboratory at 
MGH, weakening selected memories may be 



Once called battle fatigue and shell shock, 
PTSD is now considered an anxiety disorder 



that can develop not just in combat veterans, 
but also in survivors of rape, childhood abuse, 
car accidents, and other traumatizing occur- 
rences. These memories are easy to acquire; 
Most of us can recall where we were and what 
we were doing on September II, 2001, far more 
vividly than the events of September 10, 2001. 
The challenge. Pitman says, is how to tame 
seemingly indelible traumatic memories. 

The answers to this puzzle may lie within 
the brain itself. Research suggests neurotrans- 
mitters released from the brainstem during 
stress play a key role in emotional memory. Peo- 
ple with PTSD have been found to have lower- 
than-normal levels of Cortisol and higher than- 
average levels of noradrenaline, a ratio that may 
enhance learning and memory. This chemical 
pattern appears to improve the transfer of trau- 
matic events from short-term into long-term 
memories, a process known as consolidation. 

In people with PTSD, says Pitman, "the emo- 
tional arousal and biological and neurological 
changes that accompany trauma may burn 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



memories of the event into the brain so 
deeply that they keep coming back." 
When traumatic memories resurface — 
triggered by a sound, smell, or other stim- 
ulus associated with the initial event — 
they may create additional biochemical 
changes that engrave them in the brain 
more deeply. This recall and repetition of 
the original memory is called reconsohda- 
tion. It, in turn, may lead to a greater 
likelihood the memories will resurface. 

This biochemical process may help 
explain why even the most successful 
therapeutic approach to PTSD — cogni- 
tive behavioral therapy — yields lasting 
symptomatic improvement in only about 
half of those who receive it. Researchers 
elsewhere have conducted experiments 
designed to quell PTSD at the cellular 
level in rats. ConsoHdation builds — and 
reconsohdation maintains — connections 
between neurons that are mediated by a 
protein. In an attempt to prevent recon- 
sohdation, researchers injected stressed 
rats with anisomycin, a drug that inhibits 
the synthesis of this protein. Rats given 
anisomycin after trauma showed less fear 
when exposed to stimuh. 

Pitman's laboratory has been study- 
ing how pharmaceuticals affect memory 
consolidation and reconsolidation in 
humans. In one noteworthy trial. Pitman 



and his colleagues gave the beta-blocker 
propranolol to 18 people who arrived at an 
emergency department following a trau- 
ma. The anti- adrenaline drug replaced 
anisomycin, which is too toxic for human 
use. "There's evidence that a certain level 
of adrenergic activity is required for 
memories to be consohdated," explains 
Pitman. "Because propranolol can block 
adrenergic activity, it might also interfere 
with memory consohdation." 

The results were stunning: The treat- 
ment group received just a ten-day 
course of propranolol, beginning within 
six hours of the traumatizing event. 
Three months later, participants lis- 
tened to audiotapes in which they 
described their initial trauma. People 
with PTSD typically have strong psy- 
chophysiological responses during this 
procedure: sweating, muscle twitches, 
accelerated heart rate. Yet subjects who 
had received propranolol didn't show 
such physiological responses, compared 
with 23 controls. "From that," says Pit- 
man, "we inferred that their traumatic 
memories had been weakened." 

His team's findings made headlines, 
with reports trumpeting the promise 
of an effective new PTSD treatment. But 
critics expressed alarm that obhterating 
memories might prevent people from 



working through trauma and, worse, 
eliminate what it means to be human. 

Such concerns, suggests Pitman, are 
premature. His findings didn't show that 
traumatic memories had been erased alto- 
gether, but rather dulled. "We have yet to 
encounter a person to whom we've given 
propranolol who says, 1 don't remember 
the trauma at all anymore,' " he says. And 
despite the Hollywood comparisons, none 
of his subjects' other memories are erased. 
"People wonder what would occur if they 
were in our lab talking about their trauma 
and they thought about their dog," he 
says. "Would they end up forgetting their 
dog? We don't have nearly that power." 

In fact. Pitman stresses that his 
results, while promising, are prelimi- 
nary. He hopes to further our knowl- 
edge with additional research. His 
team recently received a large grant 
from the U.S. Department of Defense to 
investigate about a dozen drugs with 
the potential to inhibit memory recon- 
solidation in animals and humans. If the 
research is successful, says Pitman, such 
pharmaceuticals "may someday provide 
an alternate and potentially more effi- 
cacious way of treating PTSD." ■ 

Jessica Ccrretani is assistant editor of the 
Harvard Medical Alumni Bulletin. 



Probing False Memories 



The image of little green men spiriting away victims to a space- 
ship for a battery of unpleasant tests is a scene out of science 
fiction. But for some people, "memories" of alien abduction feel 
all too real, says Roger Pitman, director of the PTSD Psycho- 
physiology Laboratory at Massachusetts General Hospital, who 
has studied how the belief of trauma relates to symptoms of 
post-traumatic stress disorder. 

The physical responses of people with established PTSD — 
sweaty palms and a racing heart, for example — have been cited 
by some as "proof" of the veracity of recovered memories in peo- 
ple who experience similar symptoms. Working on a team led by 
Richard McNally, a Harvard psychology professor, Pitman and 
others challenged the significance of these reactions by testing the 
physiology of people with false memories. Because it's difficult to 
authenticate most recovered memories, such as those of childhood 
abuse, researchers chose o memory they suspected to be untrue: 
that of alien abduction. Evidence suggests that people who claim 
to have been abducted by aliens have instead experienced sleep 




paralysis, in which a person awakens during REM sleep to tempo- 
rary muscle paralysis and hallucinations. 

McNolly, Pitman, and their colleagues looked at ten people who 
believed they had been abducted by aliens. The subjects described 
their alleged alien encounters; their stories were recorded and later 
played back to them while researchers monitored their heart rate 
and other indicators of stress. The team's findings came as a 
surprise: People who claimed to have been abducted exhibited 
stronger psychophysiological reactions to the abduction recordings 
than they did to positive and neutral recordings, compared with 
1 2 controls. These responses were similar to those that occur in 
people with established PTSD when they recall traumatizing events. 

The results aren't proof of alien abduction, Pitman says. Rather, 
the feelings of fear and helplessness that can accompany sleep 
paralysis may help explain the subjects' reactions. "A strong 
physiological response during sleep paralysis may consolidate 
the memory of what the person was imagining at that time," he 
explains, "even though that memory is false." ■ 



24 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Harv'^arrJ Medica 

ALUMNI BULLETI^ 



presents 

'A USEFUL {YET SLIGHTLY IRREVERENT] 




TO MEMORY 

PRESERVATION 




WHENEVER I VISIT MY DOCTOR, after we have finished with 
the usual blood-pressure and weight-loss scripts, I ask him what 
he's doing to keep his mind sharp. Inquiring on this topic is like ask- 
ing someone to show a couple of snapshots from his last vacation. 
The rest of the world then waits for as long as it takes. 

Dr. Q., my specialist, has a desk littered v/ith pill bottles. He pops 
supplements between patient appointments, one to two dozen pills 
a day, but the particulars change each time we meet. The most 
recent combination (as far as I can recall) included high-dose fish 
oil, several amino acids, coenzyme QIO, thyroid hormone, testos- 
terone, and vitamins C and D. He is off vitamin E and beta- carotene, 
disappointed in ginkgo, and reconsidering Zocor since he read a 
study linking statins to memory loss. He lifts weights and carries 
index cards wdth facts he commits to memory. To improve praxis, he 



IllUSTRATIONS FOR THIS ARIICIE RYAN SNOOK 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 27 




more than $225 million was spent 
as My Brain Trainer and Mind Spa. 
down additional neural pathways. 



likes to draw his patients' blood himself in the 
office. He is a marvel. 

After each consultation, I rush home, take out 
my seven-day pill dispenser (fastidiously packed 
with my own supplements) and stir the contents 
with a forefinger. Royal jelly goes out, curcumin 
powder goes in. The recipe for a perfect brain is 
always in flux. 

But I don't really need my doctor for this 
advice — there are dozens of other doctors out 
there willing to give it, in lists with such deci- 
sive titles as "Eight Essential Strategies for 
Keeping Your Mind Sharp and Body Young," 
"Nine Strategies to Improve Memory," and "Ten 
Steps to Better Memory in Your Seventies." 
Each author is dead sure. But you see the 
dimensions of the problem already: no one can 
agree on a number. 

One could begin with "smart drugs." They 
may enhance cognition, and pharmaceutical 
companies are sprouting up everywhere to com- 
pete for them. It's like an Iron Chef smackdown, 
with contestants grabbing dishes from the hot 
stove and racing them to the patent office for 
judges to taste. 

Smart drugs are supposed to increase brain 
metabolism, improve cerebral circulation, and 
quash free radicals. There are calcium-channel 
modulators, nicotinic-receptor partial agonists, 
pyrrolidone derivatives. Don't forget the "build- 
ing blocks of life" — the amino acids, especially 
tyrosine and phenylalanine. We can take 
lecithin and l- carnitine, inositol, vasopressin, 
and lipid-lowering statins. The selective sero- 
tonin-reuptake inhibitors may cause hippocam- 
pal neurogenesis — though they also cause 
frontal apathy, or "Prozac poopout." 

Years ago, a nurse in a hospital where I used to 
work ran a thriving underground business in 
grape pip extract. Now you can buy it online, 
purified and ten times as costly. For those who 
can't swallow pills, the aroma of peppermint has 
been shown to improve performance on a Cogni- 
tive Research Computerized Assessment Battery. 

Dietary factors are earthier than nootropics, 
and you don't have to order them from specialty 
stores. The well-stocked pantry carries every- 
thing. You've got your fruits and vegetables, your 
whole grains, your omega- 3s. Red wine with 
resveratrol is recommended nightly. Take one to 



two glasses, but not more; this could qualify as 
alcohol abuse — which would damage the very 
memory you're trying to preserve. 

Then there are the many varieties of exercise. 
Physical exercise, of course, has been popular 
since the Socratic academy. It is cheap and 
healthful, with only a few caveats, such as avoid 
football, boxing, and skiing without a helmet. 
Aerobics are supposed to increase brain-derived 
neurotrophic factor and hippocampal neurogen- 
esis and to decrease prefrontal shrinkage. The 
devil lurks in the details, though. Panting non- 
athletes, checking their pedometers, want to 
know: exactly how many laps, how many sets, 
how many summits? Here experts are back to 
their disagreeing numbers — half an hour, three 
times a week; sixty minutes, six times a week; 
daily, for as long as you can bear. This much is 
vaguely clear: more is likely better. 

Social exercise may be effective, too. In one 
study, ten minutes of pleasant personal interac- 
tion each day increased Mini-Mental State Exam 
scores as much as the same amount of intellectu- 
al study. I find this heartening. It speaks well of 
our species to think that a dozen friends are 
worth a dozen logic problems. 

There is also exercise for the brain itself: In 
2007, more than $225 million was spent by the 
hopeful and the despairing on brain-fitness soft- 
ware such as My Brain Trainer and Mind Spa. 
The theory is that math, logic, and memorization 
problems lay down additional neural pathways. 
Six months after enrolling in one memory 
enhancement program, a group of 60- to 90-year- 
olds without dementia tested no better than 
their non- enrolled peers. But they were much 
less worried about themselves, which is worth 
the price of admission. Some of us will always 
prefer friends to brain exercises, but that is a 
matter of taste. I won't denigrate computer games 
if you respect the gossip I hve for. 

If you are inclined to invasive techniques — 
fatty-cheek-pad implants instead of moisturiz- 
er — there is deep brain stimulation. If you are 
less inclined, there is poetry. Alliteration and 
repetitive consonant sounds cause easier 
retrieval of similar sounding phrases. So do 
mnemonics, associations, and chunking infor- 
mation into smaller categories. Greek orators 
memorized long speeches by visuahzing them- 



28 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



by the hopeful and the despairing on brain-fitness software such 
The theory is that math, logic, and memorization problems lay 




e' 



'(A 



•f- A^, 



"^K 



$> 



9x3799 + 92 = ^^^'^ 





selves walking a 
familiar road, linking 
sequential landmarks with 
sequential points they wanted to make. 
Recall was as simple as a mental walk home. 

Finally, for those who prefer no effort, there is 
the absence of exercise altogether. Ninety- 
minute daytime naps have been found to 
increase long-term memory consolidation. 
Unfortunately, they also make it harder to sleep 
at night, which will decrease long-term memory 
consolidation. On this topic, there is no god. 

To what end all these efforts? What comes 
from supplemental, nutritional, aerobic, neuro- 
surgical, Grecian, sociable, slow-wave strate- 
gies? Not better memory, at least not in a simple 
way. First of all, the brain is more complicated 
than our efforts to master it; there are a multi- 
tude of memories to worry about losing. We 
need short-term working memory, but we also 
need long-term declarative and procedural 
memory. Second, the act of remembering fol- 
lows several stages: acquisition, consolidation, 
and retrieval. Each memory type and each stage 
is differentially sensitive to age and insult. 



Therefore one fix 
cannot fix all. You 
need to spend the rest of 
your life in repair. 
When my doctor and I are sitting across his 
pill- addled desk, there is a question I have 
never brought up. It may be too plaintive for a 
specialist. Why do we take memory to be the 
most important measurement of human worth? 
It's as if we judge the value of our minds to be 
the sum value of our selves, and no other mea- 
surements count. Dementia is tragic, but there 
is more to people than acquisition, consolida- 
tion, and retrieval. In my dotage — when I may 
no longer be able to learn what I should, and 
when I cannot recall what I want to — this is 
what I hope for; that someone I love will lead 
me by the hand to a place outdoors with flow- 
ing water and a waiting dog. We will sit 
together, listen to the water, and stroke the 
dog. In that place, I like to think, we will be 
happy — whether we remember it or not. ■ 

Elissfl Ely '88 is a psychiatrist at the Massachusetts 
Mental Health Center. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



29 



think 



of it 



One prescription for keeping the brain active may be quite 




,#^ 




■ i r i^ ' IM .■^-» < ^ ' «ilJLU.i-J iwli •^-^«'» 




simple: meditate, hy Jessica Cerretani 



DOING CROSSWORDS, LEARNING A LANGUAGE, AND 
engaging in stimulating conversations may all help preserve 
brain function. But research suggests an intriguing — and seem- 
ingly contrary — approach to memory enhancement: thinking 
about nothing. That's the finding of Sara Lazar, an HMS instruc- 
tor in psychiatry, and her colleagues at Massachusetts General 
Hospital. Their research suggests that regular meditation may 
change brain structure in positive ways. 

It's clear that meditation — a concentrated focus on the present 
moment — can increase relaxation. But its benefits may not end 
there. "Meditation appears to have profound effects on attention and 
emotion," says Lazar, vv^ho has practiced meditation for more than a 
decade. "It can color the entire way one sees the world." A growing 
body of evidence supports this claim, showing links between 
regular meditation and increased empathy, attention, and focus. 

Such changes, Lazar's team posited, should be evident in the 
physiology of meditators. "We suspected that meditation alters 
the very way the brain is wired," she says. To investigate, they 
recruited 20 men and women who regularly practiced Insight 
meditation, a technique that employs mindfulness, the nonjudg- 
mental awareness of the present. While previous studies have 
centered on Buddhist monks, who meditate for hours at a time, 
Lazar's subjects were everyday people. They practiced an average 
of 40 minutes of meditation — in this case, paying attention to 
their breathing and physical sensations without trying to change 
them — on most days of the week. 

Using magnetic resonance imaging, the researchers compared 
brain scans of the meditators to those of non-meditating 
matched controls. They found that brain regions associated with- 
attention, interoception, and sensory processing — namely, the 
prefrontal cortex and right anterior insula — ^were thicker in sub- 
jects who meditated than in those who didn't. 



The study, published in ISleuroReport several years ago, con- 
firmed what Lazar already suspected: When it comes to the 
brain, she says, "it isn't just 'use it or lose it,' it's 'use it — and it 
grows.' " Previous studies have shown that other types of regular 
practice, such as learning to juggle or playing a musical instru- 
ment, are also associated with increased brain volume. Much the 
way physical exercise builds muscles, so too does mental training 
help shape the brain. 

The significance of this brain growth is stUl unclear but may 
have implications for memory preservation, says Lazar, whose 
team is currently conducting a cross- sectional study of medita- 
tors vvdth increased cortical thickness to determine how they 
fare in tests of memory and attention. A longitudinal study, in 
which subjects' brains will be examined both before and after 
learning to meditate, is also in the works. 

The potential value of meditation may be greatest for age- 
related memory loss: Lazar points out that increased prefrontal 
cortical thickness was most pronounced in older study subjects. 
"The 50-year-olds who meditated had the same thickness as the 
20- to 30-year-old meditators and controls," she explains. "That 
suggests regular meditation may slow rates of the cortical degen- 
eration that comes with age." 

Whether that means doctors' new mantra should be, "Medi- 
tate for 40 minutes and call me in the morning" remains to be 
seen. So does the effect of other types of meditation and yoga on 
brain structure, although Lazar believes they may have similar 
benefits. What is certain is that meditation has officially made 
the leap from the province of yogis, monks, and_New Age enthu- 
siasts to the research laboratory — with promising results. That's 
worth our attention. ■ 

JcssicaCcrrctani is assistant editor o/f/ie Harvard Medical Alumni Bulletin. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 31 











1 




1 




- 





M 

i 



I 



w/'V/////'m'' 



EYEGLASS 

SEDATE 

FLORIDA 



C^ 






c» 


<^ 


o 





^ 





d 


o 


• 





Memory Splat Mat 

hy Alice Flaherty 

WHEN TO TAKE THIS TEST: People who eat breakfast score higher on memory tests than 
those who skip the morning meal, so what better time to test your \\dts? 

WHAT THIS TEST DOES: Tells you which of the three Ds is causing your poor memory; 
dementia, depression, or . . . congenitaUy low IQ. Anxiety can be lumped with depression. 

WHAT YOU NEED: Your napkin and a pencil for recording answers. Don't write on this 
splat mat, because if you really have lost your memory, youll want to refer to the mat 
again and again. 

Before you begin, look at the three words in the coffee stain to the left for five seconds. Then cover them 
M/ithyour cereal howl and take the rest of the test. 

1. How old are you? 

2. In 60 seconds, name all the animals you can think of. 

3. Name the object in each of the pictures to the right. 

4. What do those pictures have in common? 

5. Define ibis, ibex, and imbrogUo. 

6. Who notices your memory lapses more often — ^you, or others, such as your 
spouse or boss? 

7. Name the seven dwarfs in Disney's Snow White and the Seven Dwarfs. (Skip this 
question if you weren't born in the United States.) 

8. Do you have more trouble starting projects than you did three years ago? 

9. Have you recently lost interest in things you used to enjoy, such as 
sex or television? 

10. Does a word you were groping for come back spontaneously later? 

11. Remember this: "Frank Jones's feet were so big, he had to put his pants on 
over his head." 

12. Without moving your cereal bowl, write down the three words that it co\'ers. 

13. Do you have more trouble making decisions than you did three years ago? 

14. Complete the pattern in each series in the two figures to the left. 



AliceFlaherty V4, PhD, is an HMS assistant professor of neurology at Massachusetts General Hospital. 



"«||mK«MWM«r««pwiinii 



it 



i i 



'f 

A 



i; 

i I 



(ifKffi^m^: 



'W 



mmmiix 




'- 









-isim^W 








t « 




T 



ANSWERS 

A. The Theory Behind It All 

People with dementia are less aware than others that their 
memory is impaired — and worry less about it. Depression and 
anxiety cause more trouble with memory recall than with 
encoding, so memory problems provide good diagnostic clues 
for both. Memory loss from depression stems from diversion of 
attentional resources to managing the illness. It is reversible. 

B. Scoring 

Points are divided into three categories; 

B = baseline low intelligence; D = depressed; S = senile 

1. Age: 1 D point if younger than 55,1 S point if 
you're not sure. 

2. Verbal fluency: If fewer than six animals, 2 S points; 
if between six and twelve animals, 1 S point. 

3. Wig, worm, wheelchair. 1 S point for each error. 

4. Their names all start with "w." If your first thought was that 
they all have to do with aging and death, get 1 D point. 

5. Roughly, a bird, a gazelle, a mess. If you didn't hove 
any idea about any of them, get 1 B point. Word 
recognition is preserved in early dementia. 

6. If you notice and worry more about your lapses, 

1 D point. If others do, 1 S point. Most people who 
are anxious about their memory do not have dementia. 

7. fHappy, Grumpy, Sleepy, Sneezy, Bashful, Doc, and 
Dopey. If you named ifewer than 3, get 1 S point. 
Sleazy was not a dwarf. 

8. If yes, 1 D point. People with mild dementia can 
start projects unless they're also apathetic; then they 
don't notice anyway. 

9. If yes, 1 D point. 

1 0. If yes, 1 D point. 

1 1 . The story was "Frank Jones's feet were so big, he had 
to put his pants on over his head." Forgetting the 
name is fine. If you didn't remember the story at all, 

1 S point. If you didn't understand why it was funny, 
1 B point. If you understand why someone like me 
might think it was funny, but you didn't have even the 
tiniest urge to laugh, 1 D point. 

12. If you completely blanked on one, try these prompts: 
(1) related to vision; (2) means calm, sort of; (3) a 
state. Now check the answers. If you forgot one or 
more, but remembered with a prompt, 1 D point. If 
the prompts didn't help, 1 S point. 

13. If yes, 1 D point. 

1 4. Star = 66; grid = CD ■ For each error, 1 B point. 

C. More Scoring 

1 . If you keep having to look back to remind yourself 
what B, D, and S stand for, that's bad but non- 
specific — add a point to all three categories. 

2. Write your scores here: B D S . If you 

see other scores already there, and they look like 
they're in your handwriting, add one S point — 
you've forgotten you took the test already. 

3. If your S score is greater than 4, you'll be tempted to 
do memory-enhancing puzzles sucn as crosswords. But 
it turns out that normal social interaction, especially 
gossip, broadly stimulates cognition as much as — or 
perhaps more tnan — Sudoku and word-find puzzles can. 

4. If your D score is greater than 4, see a doctor. 
Remember that "appropriate" depression or anxiety is 
still depression or anxiety, still weighs you down, and 
is treatable. 

D. Questions that Don't Appear on the Exam 

1 . Do you forget people's names? Everyone forgets 
names. The human brain evolved in Neolithic commu- 
nities that tended to include fewer than 150 people. 
Now, how does that compare with the number of 
people in your address book? You do the math. 

2. Do you forget where you left your keys? Sure, it's 
bacf, but it's very nonspecific. The most common 
cause of forgetting your keys is that you have 
something more important to worry about. Highly 
successful people forget them all the time; that's 
why they have personal assistants. 

3. How reliable is this test? It's approximately 
60 percent more reliable than those Cosmo 
test-your-sex-quotient quizzes. 



Pl^■ 



Mind Games 

when it comes to building a better brain, sometimes play's the thing, hy Majid Fotuhi 



CHILDREN LEARN THROUGH PLAY, whether by stacking 
building blocks or indulging in make-believe. But imagina- 
tion, recreation, and discovery needn't be relegated to the 
schoolyard. A growing body of research suggests that people 
of all ages can tone and enlarge their brains through play, 
enhancing their memories and staving off the eroding effects 
of aging on the brain. 

Word games are a fun — and effective — way 
to challenge your brain. In one study, for 
example, a team of researchers at the 
Columbia University College of Physi- 
cians and Surgeons discovered that 
elderly people who engaged in 
brain- stimulating activities such 
as crossword puzzles remained 
sharper for a longer time than 
those who didn't. 

In fact, improving your 
vocabulary and memorizing 
passages from books are among 
the easiest and most efficient 
ways to enhance your brainpow- 
er. Memorizing a page of poetry, 
hke solving puzzles, stimulates both 
the temporal and the frontal lobes. 
And researchers believe that if you chal- 
lenge your brain by learning a new lan- 
guage, new synapses form, thus helping tone 
the very parts of your brain that can wither with age 

The games needn't be word oriented. Just as physical exer- 
cise builds muscles, learning and practicing new skills pro- 
vides a neural workout that helps bulk up the brain. Neuro- 
scientists at the University of Hamburg in Germany studied 
the brain images of a group of adults before and after they were 
taught how to juggle. After three months, the jugglers' brains 
had increased in size in the area used for hand- eye coordina- 
tion and motor activity — the occipitotemporal cortex. 

Playing music has similar effects. If you had never studied 
music and were to begin playing the piano today and practiced 
every day, the parts of your brain attuned to music apprecia- 
tion and hand movement would develop and mature. As you 




struggled to play the correct notes, you would create new 
synapses. And after just a few months of regular practice, the 
difference in the size of the areas of your cortex hnked with 
appreciating and learning music, such as the right frontal lobe, 
would be noticeable on an MRI scan. 

Physical play itself can boost brainpower, particularly if it 
involves learning and memorizing a sequence of 
movements, such as sports maneuvers, dance 
steps, and tai chi poses. The very act of 
exercise increases hippocampal levels 
of brain-derived neurotrophic factor, 
protein that improves neuron 
health and helps synthesize more 
synapses. Playing with others — 
whether team sports or board 
games — involves social inter- 
action, which is also linked 
with better memory. 

And don't forget to employ 
games as memory devices: Use 
your imagination to memorize 
hsts, make associations, and cre- 
ate mnemonics. Medicine is filled 
with mnemonics. To remember the 
^ superior thyroid artery branches, for 
example — muscular, infrahyoid, superi- 
or laryngeal, sternomastoid, cricothyroid, 
and glandular — some doctors simply recall 
May I Softly Squeeze Charlie's Girl? 
So remember this: When it comes to preserving memory, 
kidding around can help you play for keeps. ■ 

Majid Fotuhi '97, PhD, is an assistant professor of neurology at the Johns 
Hopkins University School of Medicine, director of the Center for Memo- 
ry and Brain Health at Sinai Hospital's LifcBridgc Health Brain & Spine 
Institute, and a clinical i.nstructor in neurology at Harvard Medical 
School. His most recent book is The New York Times Crosswords to 
Keep Your Brain Young: The 6-Step Age-Defying Program 
(St. Martin's Press, 2008). The "Brain ^uii' crossword puzzle is reprinted 
from Fotuhi's hook with permission. The author of the puzzle, Michael 
Shteyman, is a student at the University of Maryland School of Medicine. 



34 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Brain Quiz by Michael Shteyman 



ACROSS 

1 Stay positive and show a lot of 

37-Across (2 wds.) 
5 Endorphin, released during 

exercise, can be classified as 

this type of compound 
9 Leptin will not be able to do 

its job if this link stops working 

(2 wds.) 
1 Entered (2 wds.) 

12 Prefix after milli-, nano-, and pica- 

13 Live and breathe 

14 One reason for the buildup 

of amyloid plaques in the brain 

16 Teachers' org. 

1 7 Opposite of "relaxed" 

20 Affected by unhappiness, as a 

person with depression 
22 Chocolate, ice , and candy 

(foods you shouldn't eat every day) 
24 Rub out, as text 
26 Physicians' degs. 
28 Beginning 

31 Yang's counterpart 

32 Chemical formula for water, 
spelled out letter by letter 

34 Vegetable with antioxidant and 
anti-inflammatory properties 

35 Sleep disorder that deprives the 
brain of oxygen 

36 Hemoglobin deficiency that can 
contribute to memory problems 

37 Positive outlook on life that can 
help prolong the health of your 
hippocampus 

38 Finis (2 wds.) 

39 leg syndrome (disorder that 

can interfere with your ability to 
sleep well) 

DOWN 

1 Kind of diet that can raise your risk 
of a heart attack (2 wds.) 

2 E, antioxidant compound 

implicated in better brain function 
in the elderly 

3 Cortisol, adrenaline, or leptin 

4 Railroad worker Gage with 
frontal lobe damage 



6 "Old dogs" can learn new tricks 
because the brain is flexible and 

7 DHA is on example of ^-3 fatty 

acid, the best food for the brain 

8 What you should do to improve 
your hand, eye, and foot 
coordination 

1 1 Meditation is one way to distract it 

from your daily thoughts 
15 Purple fruit rich in antioxidants that 

help fight inflammation 

18 Planet between Venus and Mars 

19 Captain's cry for help 
21 Assistance 

23 What you can do to increase the 
levels of brain-derived neurotrophic 
factor, or BDNF, in your brain 



25 Limbic lobe is responsible for its 
production 

26 Certain brain scans, for short 

27 Contact point between brain cells 

28 Trying to lose weight (3 wds.) 

29 Early morning phenomenon 

30 Emotional or physical injuries that 
can play a role in memory problems 

32 Anxiety and stress can affect this 
organ in your body 

33 Overweight, as people with a 
higher risk of hypertension and 
Alzheimer's disease 

The answers can be found at hffp:// 
alumnibulletin . med. harvard, edu/ 
bulletin/autumn2008/solution.php 



1 




2 




3 




4 




I 


5 


6 




7 




8 


■ ■ ■ 


■ 


1 


■ 


■ ■ 


9 
















1 


10 












■ ■ 


1 




■1" 


■ 




■^■^ 


12 










13 










1 


14 


15 




■ ■" 






■ 


1 




■I ■ 


17 


18 




19 




1 


20 


21 




22 


23 








■ 


■ 


■ 


■ 


■ 


1 


■LEa 


24 








25 


1 


26 




"■ 


28 




29 




30 


Pl ■ 


1 






M" 




■ ■ 


32 




33 


34 










1 


35 










■ 


■ 




■I 


■ ■ 


36 












1 


37 
















■ ■ 


■ 


1 


■ ■ ■ ■ 


38 












I 


39 


















.s>^ 






6- 



s/, 



c 



-f 



^^. 



'^^ 



^. 



HE WAS CLIMBING THE 

mountain again. He could feel his feet navigating the 

craggy outcroppings, his hands gripping the rocks. But Robert 

Stickgold, a sleep researcher and an associate professor of psychiatry at 

HMS, wasn't on Camel's Hump; he had reached the summit of the Vermont 

peak earlier that day. He was asleep in bed — but the memory of his trek wouldn't 

fade. Even when he awoke during the night and went back to sleep, "I still found myself 

dreaming of the chmb," he says. "I had the profound sense that this was somehow important." 

Perhaps, he mused, those recurring images and sensations were his brain's attempt to help 

his body remember how to traverse the mountain. When he returned to Boston, Stickgold shared 

his suspicion with his students; that sleep-onset, or hypnagogic, dreams — the thoughts and images 

that run through our minds just as we fall asleep — play an important role in memory and learning. 

Studying the idea, however, posed a challenge. Stickgold knew he couldn't just take a group of 
subjects mountain climbing. His students suggested a simpler — and safer — solution: Tetris, an 
addictive computer game that involves the repeated positioning of falling shapes into flush lines. 
Those who had played the game often remembered dreaming about it later. 

In the study that ensued, 27 participants played Tetris on and off for three days. Stickgold's team 
then monitored their hypnagogic dreams. All of those who recalled their dreams reported seeing 
the same falling Tetris shapes. They also improved their Tetris-playing skills over the course of 
the study. Yet the findings, published nearly a decade ago, remain significant not only for 
showing what dreams the subjects had, but who had them. Five amnesiacs had been 
included in the study, mostly as a nod to a student who wanted to research amnesia 
but couldn't obtain funding. Surprisingly, three of the five also reported dream- 
ing of falling shapes. And while the amnesiacs didn't improve as much as 
the other subjects, at least one knew which computer keys to 
press — even though she couldn't recall ever having 
played the game. "This," says Stickgold, 
"suseests that the 



1> 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



37 



♦ ^ 



ta 



Without a full night's sleep, memory, 
attention, focus, judgment, reaction 
time, and learning all suffer. 



hippocampus, which is damaged in amnesiacs, 
isn't the part of the brain being used to con- 
struct hypnagogic dreams." 

It may also explain why hypnagogic dreams 
aren't just episodic memories, which are con- 
trolled by the hippocampus. If they were, sub- 
jects would remember more details of the original 
experience, such as the room in which they 
played Tetris. The fact that they don't dream 
about these details suggests what Stickgold calls 
"a brilliant evolutionary gimmick": Our brains 
pinpoint the most important information — 
repetitive activities such as positioning the falling 
shapes or climbing the mountain — and discard 
the rest. "It may be that sleep has evolved to 
extract meaning and improve learning," explains 
Stickgold. "That's why dreams are always mean- 
ingful, even when they seem silly to us." 

Dreams that occur during deeper, rapid eye 
movement (REM) sleep also have something to 
teach us, although the lessons may be less ob\'ious. 
Imagine you're driving through an intersection and 
another car runs a red light. There's no collision, 
but it's a close call. That night, you dream you're 
playing bumper cars with your son and you're feel- 
ing unhappy. The message from your brain, says 
Stickgold, isn't that you hate amusement parks, 
but that you should be more vigilant behind the 
wheel. Because the hippocampus is not involved in 
REM sleep, the brain is unable to access episodic 
memories during this phase. The resulting dreams, 
while seemingly bizarre, still serve as warnings 
and lessons. "The real purpose of the relationship 
between memory and sleep," he says, "may be to 
inform us not about our past but about our future." 

Stickgold's team continues to investigate that 
relationship. One study involves playing a 
recording of related words — such as bed, night, 
and snooze — for subjects, then testing them later 
on their recall. The word subjects tend to remem- 
ber most — sleep — isn't even on the hst. The imph- 
cation, he says, is that our brains fill in gaps to 
retain the gist of something important, particu- 
larly after a night's sleep. 

Other research by Stickgold's team suggests 
that the brain requires three stages for optimal 
memory recall — and that adequate sleep is inte- 
gral to this process. During the first stage, the brain 
forms a memory, a phase that depends on about six 



waking hours to occur. If we nod off too soon, we 
lose that memory. For the second stage, we need at 
least several hours of shuteye to edit memories and 
sharpen learning. In the third stage, edited mem- 
ories become stabilized and enhanced, allowing 
the brain to perfect previously learned skills. 

Perhaps one of the more intriguing areas of 
research on Stickgold's agenda is the hnk between 
sleep disturbances and mental health. "Every 
major psychiatric disorder has sleep disturbance 
as one of its characteristics — and it's assumed 
that mental illness causes these disturbances," he 
says. "But I beheve the relationship is at least bidi- 
rectional." He points to a study he's pubhshed 
that found schizophrenics who learn a simple task 
appear to show no overnight improvement in that 
skill, a possible sign that they may not process 
memories properly during sleep. Stickgold hopes 
to someday discover what function sleep and its 
effects on memory and learning may have in con- 
ditions such as depression, bipolar disorder, and 
attention deficit hyperacti\'ity disorder. 

So how much sleep do we need for optimal 
memory? "Simply put, we just don't know," 
Stickgold says. Some studies have found a 90- 
minute afternoon nap to be more effective than 
six hours of nighttime sleep at impro\'ing learn- 
ing; other research suggests that consistency 
over time may be more important than the 
amount of sleep we get on any given night. One 
thing is clear: Sleep is necessary for optimal 
brainpower. Without a full night's sleep, memo- 
ry, attention, focus, judgment, reaction tune, and 
learning all suffer. Studies by Charles Czeisler, 
the Baldino Professor of Sleep Medicine at HMS, 
have graphically illustrated those consequences 
in medical residents: fatigue-related medical 
errors, needle sticks, and motor vehicle crashes. 

Shuteye has other benefits, too. There's evi- 
dence linking sleep deprivation to decreased 
immunity and weight gain. The bottom line, 
says Stickgold, is that some amount of sleep is 
essential for good health. "The most depressing 
thing," he laughs, "is that I'm spending my entire 
career proving that my mother was right — about 
sleep, anyway." ■ 

Jessica Cerretani is assistant editor of the Harvard 
Medical Alumni Bulletin. 



38 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Recall Buttons 




Combat retention deficit disorder with these tips, hy Aaron P. Nelson 



EVEN MEMORY EXPERTS CAN BE FORGETFUL. MY WIFE AND I, BOTH 

neuropsychologists at Harvard- affiliated hospitals, once 
drove 50 miles before realizing we had neglected to pack bur 
six-year-old daughter's security blanket. Rather than face a 
week of her despair, we returned home. And there, in our 
driveway, we found our other car with the key left in the 
ignition — and the engine running. 

An old Chinese proverb tells us that the palest ink is better 
than the strongest memory. Although memory glitches may 
plague us all, we can still take steps to boost our powers of 
recall. Here are a dozen steps I prescribe to my patients — and 
try to follow myself. 

^, Get Moving 

Research shows that people who engage in regular exercise 
tend to stay mentally sharp into their eighties and beyond. 
Led by Eric Larson 73, a team of investigators at the Univer- 
sity of Washington found, for example, that people aged 65 or 
older who exercised three or more times a week had a lower 
risk of dementia than their less active counterparts. 

Exercise aids memory in several ways: It strengthens the 
lungs and the cardiovascular system, a combination that 
helps ensure the steady delivery of oxygen to the brain. Phys- 
ical activity helps minimize the risk of diabetes, high choles- 
terol, high blood pressure, and stroke — all diseases that can 
impair cognition. Exercise may also increase connections 
between brain cells and enhance neurotransmitter function. 
Eor good brain health, engage in at least half an hour of mod- 
erately vigorous exercise most days of the week. 

|P, Stay Mentally Engaged 

Your mind thrives on new challenges and learning experiences. 
In the MacArthur Foundation Study of Aging in America, 
researchers found that the characteristic most strongly linked 
with good mental functioning was level of education: Experts 
suspect that school-based education fosters a lifelong habit 
of learning. And education in the broader sense, outside class- 
room walls, buHds cognitive reserve, or the resilience of the 
brain to withstand neuropathological assault. 



Exercising your brain with challenging activities is 
believed to stimulate communication between brain cells. 
Some of these activities are obvious, such as doing crossword 
puzzles, playing chess, reading, and taking classes. But men- 
tal stimulation can also come from any deviation from your 
daily routine that makes you think, such as taking an alterna- 
tive route while driving. Try to develop new skills — or relearn 
old ones you may have set aside; that trumpet stowed in your 
closet may be a good place to start. 

tA, Don't Smoke 

In studies of memory and cognitive function, smokers per- 
form worse than nonsmokers. It's unclear whether smoking 
directly muddles memory or is associated with memory loss 
because it causes illnesses that compromise brain function. It 
is clear, however, that smoking increases the risk of stroke 
and hypertension, two conditions that impair memory. 
Regardless of the exact link, if you smoke, it's never too late to 
quit: People who stop smoking show less cognitive decline 
than those who continue. 

^^j Drink Only in Moderation 

While moderate consumption of alcohol may reduce the risk of 
dementia, excessive consumption is toxic to neurons. It is also 
a leading risk factor for Korsakoff's syndrome, a disorder that 
causes irreversible memory loss. If you are a heavy drinker, cut- 
ting back can prevent further memory loss and will usually 
lead to the recovery of some memory function. 



t^ 



Eat a Healthful Diet 



A diet rich in fruits and vegetables, whole grains, and healthy 
fats from fish and nuts is vital to maintaining brain health. 
Many fruits and vegetables are good sources of vitamins and 
other nutrients that may protect against age-related diseases 
and deterioration throughout the body. Avoiding saturated 
fats and trans fats helps keep your arteries clear and choles- 
terol levels healthy, which in turn can decrease your risk of 
cardiovascular disease and stroke, including the small "silent" 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



39 



strokes that can damage brain function. And maintaining a 
normal weight lowers your risk for illnesses such as diabetes 
and hypertension, which can harm memory. 

Aj Take Vitamins 



Taking a high-quality multivitamin and individual vitamin 
supplements can help ensure your body is getting the nutrients 
it needs. Certain B vitamins — B6, B12, and folic acid — provide 
neuronal protection and facilitate the breakdown of homocys- 
teine, an amino acid in the blood that, at high levels, can raise 
the risk of heart disease, stroke, and peripheral vascular disease. 

^, Sleep Tight 

Sleep is essential for memory consolidation as well as overall 
health. Although people vary in their individual sleep needs, 
research suggests that six to eight hours a night is ideal. 
Perhaps even more important than the amount of sleep is the 
quality of sleep. People with sleep disorders that affect breath- 
ing, such as obstructive sleep apnea, can sleep ten hours a 
night yet still feel untested in the morning. 

For some people, a good night's sleep can seem elusive. 
Developing certain habits can help: Establish and maintain a 
consistent sleep schedule and routine. Do your most vigorous 
exercise early in the day. Stay away from coffee and other 
caffeine sources after midmorning. Avoid excessive napping 
during the daytime. Shun sleeping pills unless nothing else 
works. And don't try to sleep if you're not tired — you'll mere- 
ly set yourself up for tossing and turning. 



e' 



Manage Stress 



When you're under stress, it's difficult to concentrate, and 
insufficient concentration is one of the primary causes of 
poor learning and memory. Sustained stress can impair your 
memory by altering brain chemistry and damaging the hip- 
pocampus. Although you can't control all the sources of stress 
in your life, you can temper your reactions to stress. 

Taking a brisk walk or exercising in other ways helps some 
people reduce stress levels. Listening to music, meditating, tafk- 
ing to a friend, or engaging in relaxing activities, such as gar- 
dening or knitting, can also help. If you can't lower your stress 
level on your own, you may find rehef through counseling. 



Stay Connected 



Social support — through relationships with family members, 
friends, colleagues, or caregivers — can improve cognitive 
performance in older people. And the elderly aren't the only 
ones who benefit. 

In a 2008 study of more than 3,600 people between the ages 
of 24 and 96, researchers at the University of Michigan found 



that across all age groups the higher an individual's level of 
social interaction, the better his or her mental function. A sec- 
ond study on the same cohort found that people engaged in 
social groups and those involved in sohtary intellectual activ- 
ities such as reading and doing crossword puzzles both scored 
higher in mental processing speed and working memory than 
the controls, who merely watched television. 

Social engagement may benefit your memory in several 
ways. Intellectually stimulating activities often go hand-in- 
hand with social interaction. Social relationships can also 
provide support during stressful times, reducing the damag- 
ing effects of stress on the brain. 

Protect Your Head 



Head trauma is a major cause of memory impairment and a 
risk factor for dementia. Wear a seatbelt when riding in 
motor vehicles, as car accidents are by far the most common 
cause of brain injury. You can also prevent head trauma by 
using appropriate gear during high-speed activities and con- 
tact sports. Put on a helmet when bicycling, riding a motor- 
cycle, in-line skating, and skiing. And wear a mouth guard 
during contact sports. Using this type of protective device 
can lower the risk of concussion by deflecting the force of a 
blow to the chin. 

^, Avoid Exposure to Toxins 

Reduce your exposure to toxic substances by taking sensible 
precautions. Read labels for safe handling before using paints, 
solvents, and pesticides. Test your home water supply and 
use a water filter to eliminate lead, if necessary. Have your car 
and furnace serviced regularly to minimize carbon monoxide 
emissions. Avoid sanding, scraping, and otherwise disrupting 
lead paint in older homes. If you plan to remove lead paint, 
hire a government- approved contractor. 

^^, Pursue Your Passion 

The pursuit of an abiding passion encourages you to seek new 
knowledge, connects you with people who share your inter- 
est, guards against depression, and serves as a buffer against 
stress, all of which benefit memory. Participating in some- 
thing meaningful, particularly in the context of giving to 
others, also helps engender a sense of personal efficacy — and 
the ability to make a difference can make all the difference to 
the health of your brain. ■ 

Aaron P. Nelson, PhD, is an assistant professor of psychology at Harvard 
Medical School and chief of neuropsychology in the Division of Cogni- 
tive and Behavioral hleurology at Brigham and Women's Hospital in 
Boston. He is also the author o/The Harvard Medical School Guide 
to Achieving Optimal Memory (McGraw-Hill, 2005). 



40 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



Bearing witness fosters hea. 
childhood sexual abuse. 



T1C7 £irr 
hy JfJD^ 



|ng survivors of 



iTH Lewis Herman 




IN 1970, THE YEAR I BEGAN MY 

psychiatric residency, I belonged to a 
consciousness-raising group known 
as Bread & Roses Collective No. 9. In 
those early days of the women's move- 
ment, many women came forward to 
disclose sexual violations long kept 
secret. With a new awareness, I lis- 
tened to the stories of my first 



tormented by memories of incest. 

These women and their stories had 
a powerful impact on me. After my 
residency, I began working at a store- 
front women's clinic. Before long, a 
colleague and I had collected 15 cases 
of father-daughter incest. V/e first 
published our findings in a women's 
studies journal in 1977. In the year 
before the article was published, the 
manuscript was passed hand-to-hand 
like underground literature, and we 
began receiving letters from women 
throughout the country. They all 
wrote, "I thought I was alone." It was 
then we realized that we had indeed 
made a discovery. 





m^ttsi^mmm 



if a child discloses sexual abuse, there is a 



I { )| ) / \ T rnuch better chance that the person hearing 



the story will respond in a protective way. 



At that time, the Comprehensive Textbook 
of Psychiatry estimated the prevalence of 
incest at one case per milhon. This esti- 
mate proved to be wrong by several 
orders of magnitude. We now know that 
sexual abuse of children is common and 
often has terrible consequences for 
the abused child. We also know that 
the most common perpetrators are peo- 
ple the child knows and trusts: teachers, 
coaches, clergy members, uncles, broth- 
ers, stepfathers, and fathers. (The great 
majority of perpetrators are men.) 

As the women's movement encouraged 
survivors to come forward, and as new 
research documented the prevalence of 
such abuse, we entered a period in which 
these discoveries gained sympathetic 
attention from the media. Oprah Winfrey 
set an example by coming out as a sur- 
vivor of childhood sexual abuse, and she 
has gone on to do what I regard as some 
of the best public education on child 
abuse and violence against women. 
School-based educational programs were 
developed to encourage children to teU 
someone if they were being abused. 

Today, if a child discloses, there is a 
much better chance that the person hear- 
ing the story will respond in a protective 
way, rather than shaming and silencing 
the child. Recently, the many survivors of 
sexual abuse perpetrated by clergy — not 
only Roman Cathohc but Jewish and 
Mormon, among others — increased the 
credibihty of victims by coming forward 
and enduring the rigors of court testimo- 
ny to share their stories. 

As long as victims of sexual abuse 
were shamed into silence, these crimes 
against children were essentially crimes 
of impunity. As public awareness of the 
problem grew, however, many states 
began to amend their laws to make it 
easier for child victims and adult sur- 
vivors to testify in court. In particular, 
many states extended their statutes of 
limitations in recognition of the fact 
that adult survivors might need time to 
gain an understanding of the harm done 



42 HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 








/^ 



■^^;?i<^" 






gCtiiM^.-^'^ 




to them, either because they might not 
have initially made the connection 
between their suffering and the abuse 
they endured, or because they might 
have had a period of frank amnesia. 

And thus began the controversy over 
memory. A backlash can be expected 
whenever crimes of impunity suddenly 
become crimes with possible conse- 
quences. We see this in societies emerg- 
ing from repressive regimes, when 
perpetrators of pohtical crimes — previ- 
ously immune as government workers, 
pohce officers, spies, or prison guards — 
are suddenly exposed. As the evidence 
of their crimes accumulates, they resort 
to impugning the credibility of their 
accusers. It is no different with crimes 
against women and children. 

As adult survivors of incest started 
to come forward in court, perpetrators 
countered that their accusers must 
have been brainwashed. In this render- 
ing of the story, the accusers had been 
alienated from their loving families by 
unscrupulous psychotherapists who 
had instUled false memories of abuse. In 
a cUmate of sympathy for the victims, 
blaming a third party was generally a 
more favorable strategy than attacking 
the victims directly. It also served to 



patronize and demean the victims, as it 
implied that they didn't know their 
own minds. 

When allegations of false memories 
started to appear, the media latched onto 
this novel angle for a while. We no longer 
see much in the press about false memo- 
ries, but at the height of the controversy, 
the main line of attack was the sugges- 
tion that incompetent or biased clini- 
cians were implanting memories in the 
minds of the vulnerable: children and 
unstable women. After all, why had the 
victims not mentioned the crimes earh- 
er? Much was made of the notion that 
memories of sexual abuse disappeared 
from consciousness only to be recalled at 
some later time. The impUcation was 
that a memory recalled after a period of 
amnesia was inherently suspect. 

In fact, many survivors of childhood 
sexual abuse dearly wish to forget — but 
carmot. When these people begin to 
describe the abuse, they will say some- 
thing like, "I never forgot, but I was too 
ashamed to say anything about it. I tried 
to force myself not to think about it." 
Well into adulthood, some victims feel 
so tormented by their shame that they 
cannot give voice to what they have 
always perfectly well remembered. 



Others may have partial recall. One 
patient of mine, for example, initially 
claimed she had no memories. What 
she meant was that she did not remem- 
ber the details of physical encounters 
with her father. She did have clear 
memories, however, that her father 
would leave pornography around for 
her to see, that he would continually 
tell dirty jokes, and that his lewd inter- 
est in her and other young women was 
apparent in many ways. His behavior 
was tolerated within the family; he was 
just being his quirky self. No alarm was 
raised, and no one sought to protect 
her. The patient felt alone with her feel- 
ings of disgust and humiliation. So in 
fact, she did have plenty of memories, 
but she had not yet learned how to 
make sense of them. As she explored 
the feelings her memories evoked, she 
was able to recall more details of specif- 
ic incidents of abuse. 

Run Silent, Run Deep 

A significant minority of victims do 
seem to have dense amnesia about their 
abuse for a period of time, only to recall 
it later, often through struggle and pain. 
In a study that Emily Schatzow, a lec- 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



43 



WHEN 



a person is traumatized, the 
memory of the trauma is laid down 
in an altered state of consciousness. 



44 



turer on psychiatry at Harvard Medical 
School, and I conducted with 53 female 
outpatients, we found that 28 percent 
reported a period of severe memory 
deficit. What seemed to set this group 
apart is that the abuse began very early, 
in the preschool years, and ended before 
adolescence. Also, the degree of amnesia 
seemed to be related to the level of frank 
violence that accompanied the abuse; 
the more violent the abuse, the greater 
the memory deficit. 

Two factors may be at work here. 
First, the memory functions of early 
childhood differ from those that develop 
later. Second, traumatic memories are 
not stored in the same way that ordinary 
memories are. Both of these factors serve 
to keep the knowledge of beiag abused 
out of the autobiographical narrative 
that each person ordinarily assembles. 

In the nineteenth century, Pierre Janet, 
an early student of trauma, described 
traumatic memory as an idee fixe. He con- 
trasted this with normal memory, which 
he described as "the action of telling a 
story." A memory is not truly a memory, 
he said, untU it has been recited to one- 
self and to others and taken its place in 
our personal narrative. Ordinary memo- 
ry, Janet held, is fluid, contextual, and 
autobiographical; it requires a certain 
amount of verbal processing and is sub- 
ject to voluntary retrieval. A traumatic 
memory is static, fragmentary, and non- 
verbal — one remembers sights, sounds, 
smells, and tastes — and it is not subject 
to the usual mechanisms of voluntary 
recall. It might intrude, unwanted, as a 
flashback; when sought, it might 
remain inaccessible. 

Janet's description of trauma and 
memory has held up extraordinarily 
well to the scrutiny of contemporary 
research. In the fourth revision of the 
Diagnostic and Statistical Manual of Mental 
Disorders, amnesia for all or part of a 
traumatizing event is recognized as one 
of the diagnostic criteria for post-trau- 
matic stress disorder. 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



When a person is traumatized, the 
memory of the trauma is laid down in 
an altered state of consciousness. For 
effective retrieval, the person must gain 
access to that altered state, not only 
recalling the event, but also reconnect- 
ing with the state of feeling that accom- 
panied it. Early in his career, Sigmund 
Freud used hypnosis to gain that access. 
In the many wars of the twentieth cen- 
tury, military psychiatrists discovered 
that hypnosis or the administration 
of sodium amytal could help shell- 
shocked soldiers access their memories. 
Military psychiatrists also found that 
"the action of telling a story" could 
bring dramatic relief to traumatized 
soldiers, often allowing them to return 
to battle. 

As the role of early sexual trauma 
was being rediscovered three decades 
ago, many clinicians, like military psy- 
chiatrists, were eager to get to the core 
of the problem quickly. Since then, clin- 
icians have become wiser. We have 
learned not to ask leading questions 
and to permit victims to deal with their 
memories at a safe pace. 

Various methods have been devel- 
oped to facilitate the recovery and inte- 
gration of traumatic memories. Any of 
these approaches may have value — but 
highly specialized techniques are not 
necessary. What is needed most is a 
relationship of empathic witnessing. 
This therapeutic relationship creates a 
safe context for exploring traumatic 
memories, allowing for the expression 
of intense feelings of fear, rage, and 
shame, so that the memories can at last 
be integrated into an ongoing life narra- 
tive. In this process the amnestic barri- 
ers, which are always semipermeable, 
gradually give way. Then, the trauma 
can be grieved and allowed to take its 
place in the past. 

This healing process may help the 
individual survivor come to terms with 
a past abusive experience, but it does 
not address the larger social problem of 



justice. Memory is not only a personal 
matter; as we discovered in our con- 
sciousness-raising group, it is also a 
matter of bearing witness. 

Recently, I conducted a study in 
which I interviewed survivors about 
their visions of justice. What they 
wanted most was acknowledgment, 
both of what had happened to them and 
of the harm done. They also wanted the 
family or the community they had Hved 
in to take some responsibihty for the 
neglect that permitted the abuse to 
occur, and to make amends. Just about 
half wanted an apology from the perpe- 
trator, and then only if it was accompa- 
nied by genuine empathy and remorse, 
as rarely as those emotions may occur 
in abusers. As one survivor put it, "Per- 
petrators lack empathy, or they wouldn't 
commit abuse in the first place." 

Interestingly, few of my informants 
embraced a retributive idea of punish- 
ment for its own sake. No one wanted 
the perpetrator locked up, unless he was 
considered a recidivist predator. For 
example, one of my informants had noti- 
fied the police when she discovered that 
her niece was being abused, just as she 
and her sisters had been abused in child- 
hood by the same perpetrator. At that 
point she mobihzed her sisters, and they 
supported the niece in pressing criminal 
charges. The perpetrator was convicted 
and sentenced to prison, where he final- 
ly acknowledged the abuse. My infor- ^ 
mant beUeved prison was the best place J 
for him because he was still a danger to 
the community. To this survivor, only the 
desire to protect others made the ordeal 
of court testimony worthwhile. 

Justice Deserved 



Despite legal reforms, the U.S. justice 
system continues to be unfriendly to 
adult survivors and even more stress- 
filled for child victims. If you wished to 
design a mechanism for exacerbating 
symptoms of post-traumatic stress dis- 




order you couldn't do better than a court 
of law. The adversarial system, of neces- 
sity, places the victim's credibility under 
attack. Instead of being able to tell 
their stories in their own fashion and 
at their own pace, victims must answer 
rapid-fire, yes-or-no questions, and 
instead of having control over expo- 
sure to reminders of the trauma, they 
have the reminders pressed upon them. 
It takes amazing courage for someone 
who has grown up with a perpetrator 
who was both loved and terribly feared, 
who was viewed as all powerful in the way 
that a child sees a parent as all powerful, to 
confront that person in a court of law. 



More victims would risk such a con- 
frontation, though, if the remedy the 
court afforded was anything resembling 
what victims wanted. But punishment of 
the offender is not what most are seek- 
ing. Moreover, there's Httle evidence as 
to the overall effectiveness of punishing 
and registering sex offenders. Criminal 
prosecution simply doesn't work as a 
prevention strategy. For this reason, it is 
worth considering some emerging mod- 
els of community intervention that diEer 
considerably from conventional legal 
responses. Conceptually, these models 
draw their inspiration from the restora- 
tive justice movement. 



One of these models, initially devel- 
oped in a child-protective service in 
Canada, is called family group confer- 
encing. In this model, all the members of 
a family are brought together for a formal 
meeting, each with at least one support 
person. In this way, an extended social 
network may be mobilized. Older chil- 
dren are included in the process and may 
bring a friend. The meeting begins with a 
full discussion of what happened and an 
acknowledgment of both the facts of the 
case and the harm done. Child-protec- 
tive officials also lay out the require- 
ments for an action plan to remedy the 
situation. The family group must then 
devise a plan to protect the child victim 
from further harm. An agreement is 
signed, and the respective support sys- 
tems agree on to how it will be moni- 
tored and enforced. In this process, pun- 
ishment of the perpetrator is beside the 
point. The victim's priorities are central, 
not peripheral, to the outcome, and the 
victim's community takes responsibihty 
for protective action. 

Mobilizing a community response 
may ultimately do more to develop a 
culture of protection and safety than 
prosecutions can accomplish. The pri- 
mary need, of course, is protection. For 
children the first line of protection 
appears to be a mother with the power 
to take care of them. It has been clear 
even from our earliest research on incest 
that a disabled or disempowered moth- 
er is one of the biggest risk factors for 
child sexual abuse. Any policy or inter- 
vention that promotes women's health 
and enhances the status of women ulti- 
mately protects children as well. The 
same women's movement that brought 
this problem to light is also the surest 
advocate for its solution. ■ 

]udith Lewis Herman '68 is a clinical profes- 
sor of psychiatry at Harvard Medical School 
and director of training at the Victims of 
Violence Program at the Cambridge Health 
Alliance in Massachusetts. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



45 



o^ G^o 



TH 

sma; 

STIT 
>OIC 



c^f^..eN^ 




A SEVERELY BURNED CHILD TEACHES HIS SURGEON ABOUT 




UR LIVES HOLD TRANSFORMATIONAL 
moments, fragile as spun glass. They drift for only a second and then shatter. We don't 
just feci these revelations. They hit us, like a fist. One such moment occurred for me 
halfway through the first year of my surgical residency, during a two-month stint on 
the burn service at Massachusetts General Hospital. 

All residents dreaded the burn service. The adult ward was bad, but the pediatric 
ward, known as the Shrine, was far, far worse. The Shriners Hospital in Boston served 
as the major center for most pediatric burn victims along the eastern seaboard. Its 
burn service, which the surgical residents had grimly nicknamed Crispy Critters, was 
the closest thing we could imagine to hell on earth. There, dozens of mutilated, 
suffering children huddled in one somber, sorrowful building. 

On my first day, the head nurse led me to the intensive care unit to see the big 
burns — "the eighty-percenters or higher." Before going onto the unit, we had to don 
masks and sterile scrub suits with hoods. As the translucent glass doors hissed apart, 
we entered into an alien vv^orld — an encampment. The room was bathed in the 
purple glow of ultraviolet hghts. Each child was surrounded by huge plastic drapes 
designed to wall out bacteria. Devices made whining, sucking, and bubbling sounds, 
a robotic chorus that rose up around each swaddled form. Each child resembled a 
mummy; only the shape outlined beneath layers of dressings hinted that a child might 
he buried within. Had it not been for the frenzied activity of the machines, there 
would have been nothing to suggest the larval forms were even ahve. 

I had never seen so much suffering concentrated in one place. How would I get 
through the rotation? It seemed unendurable. 



r THE ENDURING POWER OF THE SPIRIT. ~ hy Allan ]. Hamilton 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



47 



CHILD AFTER CHILD WAS RECAST INTO AN ANGEL AND 



48 



The nurse led me out of the ICU, 
known affectionately as Mummy World, 
and into Camp Chronic, the ward where 
survivors eventually arrived for endless 
rounds of reconstructive surgery. Here 
the children became living clay as sur- 
geons practiced the dreadful artistry of 
reconstructive surgery. And here the 
children began to emerge. Like geologic 
formations, they became sedimentary, 
surgical layers, recording each new tech- 
nical era, one upheaval to the next. 

It took me weeks to settle in. At first I 
felt rehef whenever I could leave the build- 
ing and breathe lungfuls of antiseptic- 
free air. I would gaze at people walking 
down the street, with bodies like sup- 
ple saplings and hands as smooth and per- 
fect as porcelain. It amazed me how utter- 
ly normal the physical world was outside. 
Entering Crispy Critters each day felt hke 
being condemned, with my heart drown- 
ing as soon as I passed through its doors. 

After some time, I began to view 
things differently. Every child became a 
small, brave experiment in courage, 
endurance, and improvisation. Gradual- 
ly, Crispy Critters seemed less like a 
bleak prison and more like a hybrid of 
laboratory and chapel. Life had been 
rendered to molten form. Child after 
child was recast into an angel and then 
sent to test the world's compassion. And 
we — the outside, unmarred world — 
repeatedly failed the test. 

Fallen Angel 

One angel-chUd stood out for me. His 
name was Thomas. His story, like those 
of so many in the institute, had a grim 
beginning. When he was about ten years 
old, he and a friend were playing in the 
rolling farm country outside Lancaster, 
Pennsylvania. They walked across fields 
that were pushing up the green promise 
of the season's first corn. From there, 
they passed through the edge of a family 
farm. As they hiked, they came across a 
footpath to the crest of a large hill, upon 
which sat a tower carrying a high-volt- 
age line. They scaled the tower, which 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



commanded a view of the whole coun- 
tryside. From its heights, the boys could 
see not only their own houses but hori- 
zons far beyond. 

What a view it must have been! For a 
moment, they must have felt like eagles. 
But Thomas slipped. He fell about a 
dozen feet and came to an abrupt halt. 
His clothes had caught on one of the 
arms of the tower. As he reached up to 
pull himself off, he touched the power 
line. Thousands of volts arced through 
his small body, shaking it convulsively. 
His body tore loose from its snag, but not 
before his clothing had ignited. He plum- 
meted more than a hundred feet to the 
ground, a flaming meteorite. His com- 
panion clung to the electric tower, too 
terrified to move. 

Smoke rising over the horizon alerted 
firefighters. They lowered Thomas's friend 
safely to the ground. Of Thomas, there 
remained little that was not burned. 
Small patches of skin remained intact 
only in his armpits, his groin, and the 
folds of certain joints. It seemed as if 
every bone had been broken. Nearly all 
his soft organs were damaged and bleed- 
ing. No one held much hope the boy 
could survive. Mercy suggested that dying 
might have been gentler. 

Thomas's life, though, continued to 
flicker. The paramedics stabilized the 
boy and rushed him to a trauma center in 
Philadelphia. There he underwent three 
operations to stem the internal bleeding. 
Then a special medical turboprop air- 
craft flew him to Boston, where an 
ambulance sped him to the Shrine. He 
arrived ready to enter Mummy World, 
swaddled from head to toe in gauze. 
Intravenous lines poked through his 
dressings Kke unruly vines. That was 
when he became my patient. 

A Fresh Start 



In the initial phases of critical burn care, 
the patient must be covered with new 
skin. This is accomplished first with 
grafts taken from fresh cadavers. 
Although the skin is dead, the thin strips 



of dermis and epithehum work beautiful- 
ly as temporary skin. Soon the patient's 
immune system vvoll reject the foreign tis- 
sue, but, with luck, the cadaver grafts will 
buy the time needed for harvesting the 
patient's skin — the autologous sldn — 
and using it to resurface the body. 

Thomas's body had an unusually 
potent prochvity for rejecting cadaver 
grafts. While most patients rejected a 
graft in ten to fourteen days, Thomas 
would slough his off within five. We'd 
have to find more skin in the hospital's 
tissue bank, then resurface his body 
again. Each time the procedure required 
six to eight hours of tedious work to 
suture the new skin grafts into place. 

The surgery was painstaking and 
wearying. Skinning a human corpse and 
sewing new skin into place hke uphol- 
stery fabric are gruesome tasks. But we 
could do httle else to save Thomas's Me. 
He rejected the second series of grafts in 
just four days. We undertook a third set, 
and a fourth set. The latter lasted less 
than 48 hours. 

It seemed unlikely that Thomas would 
survive. We simply couldn't harvest 
enough native grafts to cover his entire 
body quickly enough. We were ready 
to give up on him, more out of exhaus- 
tion perhaps than pity. But fate inter- 
vened. The boy's parents had been dev- 
astated by what had happened to their 
son. To be isolated in Pennsylvania, while 
their son's life slipped away in Boston, 
proved to be too much. Thomas's father, 
only 42 years old, collapsed from a heart 
attack and died. 

Thomas's mother called to let the sur- 
geons and nurses know her husband had 
passed away. It seemed just too much 
tragedy for anyone to bear. But his moth- 
er calmly asked whether we would be 
interested in harvesting skin grafts from 
her husband's body. 

The idea had merit. Thomas's condi- 
tion had continued to worsen, and he was 
shpping deeper into his coma with each 
bout of graft rejection. His body was 
already becoming peppered with small 
abscesses and sites of local infection. 



THEN SENT TO TEST THE WORLD'S COMPASSION. 




f 



signs that the latest cadaveric grafts 
would soon be shed. But skin from 
Thomas's father might not be rejected. 
It would not be autologous tissue, but it 
would be close. It was worth a shot. 

A Kindred Spirit 

Our surgical team flew to Philadelphia 
with crates of instruments. It was diffi- 



cult to imagine any relationship between 
the gray, cold body of Thomas's father 
and the other, near-lifeless body in 
Boston. Yet we shced the skin as thinly as 
we could, packed the translucent strips 
in sterile plastic bags, and placed the 
bags inside a refrigerated cooler for the 
return trip. 

At the Shrine, more bad news awaited 
us. During the night, Thomas had wors- 



ened significantly. Bacteria were grow- 
ing in his bloodstream. He was shpping 
into a terminal, septic coma. We felt hke 
fools, stranded on the beach with our 
picnic cooler full of skin. It seemed a 
grim, futile joke. 

In the coffee-break room at Crispy 
Critters, we debated endlessly. Should 
we just freeze the father's skin and keep 
it in the unlikely event that Thomas 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



49 



MY DAD'S JUST STANDING THERE AT THE END OE MY BED. 




survived? Finally, hope prevailed. The 
senior surgical attendings made the deci- 
sion; We v^ould cover Thomas with his 
father's skin. 

That morning we removed all the 
dead graft tissue covering Thomas. 
Painstakingly, over the next eight hours, 
we quilted his father's skin onto him. 
The grafts looked lifeless and gray. I had 
httle confidence. 

By dinnertime, we had finished. 
Fresh bandages in place, Thomas's 
comatose body was wheeled back into 
its slot in Mummy World. His vital 
signs seemed stable enough. We knew 
he had survived considerable surgery, 
but we had doubts about his physiolog- 
ic reserves. I went into the call room 
and fell asleep instantly. I had been on 
the move for more than 48 hours. 

Only seconds seemed to have passed 
before I woke up, angry and disorient- 
ed. A nurse was pounding on the call- 
room door. I looked at my watch. I'd 
been asleep for only two hours. Thomas 
was probably dying. Maybe his heart 



50 HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



had already stopped. I steeled myself. 
We'd done everything possible. It was 
time to let go. 

I opened the door, "It's, it's Thomas," 
the nurse stammered. "He's, he's trying 
to talk!" 

That simply wasn't possible. Thomas 
must be having problems with his venti- 
lator. She'd misinterpreted his respirato- 
ry efforts as an attempt to talk. Hadn't 
he been in a coma for nearly a month? 

I ran to the ICU. Not only was 
Thomas trying to speak, but he was also 
moving all his limbs — something he'd 
never done before. He was fighting his 
bandages and constraints. It must have 
been extremely painful, as many of his 
fractures hadn't yet healed. But the 
efforts were unmistakable. He was try- 
ing to pull out his endotracheal tube. 

I slipped my hands inside the plastic- 
encased arm ports, reached around his 
throat to undo the knot, and deflated 
the small balloon at the end of the tube. 
Then, daring more than hoping, I pulled 
the tube out of his mouth. 



He coughed violently a couple of 
times. Suddenly, he spoke. His voice was 
perfectly clear. 

"What happened to my father?" 

No one had uttered a word to Thomas 
about his father; he'd been unconscious 
the entire time. The nurses looked at me. 
It was my responsibihty to answer. After 
all, I'd been the one who'd removed the 
boy's endotracheal tube. 

I decided to he. "Nothing has hap- 
pened to your father, Thomas. He's just 
fine," I said. 

Thomas looked at me in confusion. "Are 
you sure?" The boy was completely lucid. 

"Yes. I'm sure. He's fine. He'll be glad 
to hear you're getting better." 

Today, I deeply regret that lie. I 
should have told him the truth right 
away. I was a young resident, though, 
and I didn't know better. I thought I 
was being kind. But Thomas knew 
something was wrong. 

"My dad's just standing there at the 
end of my bed. Why doesn't he say some- 
thing?" There was the hammer blow. 



WHY DOESN 



SAY SOMETHING?" 



For a crazy instant, I blanked out 
what had actually happened. The 
father's death. The harvest of skin. Then 
reality returned. Thomas must be seeing 
someone through the plastic, a distorted 
silhouette that reminded him of his dad. 
I looked around. No one was there. Just 
the drapes and the Ughts beyond. 

"Thomas," I asked, choking back 
tears in disbelief, "where do you see 
your father?" 

"He's standing right there," he 
answered, staring at the empty foot of 
the bed. "Hi, Dad!" he called out, and he 
feebly attempted to wave. 

One of the nurses choked back a sob. 

"Thomas, your dad passed away," I 
said. "He died three days ago. He had a 
heart attack." 

I could see the shock registering with- 
in, even beneath so many layers of ban- 
dages. Then I heard him whisper some- 
thing. I leaned over. 

"That must be his ghost then that's 
waving back at me," he said softly. 

I knew then that what Thomas saw at 
the foot of his bed was his father's spirit. 
Here was my own fragile moment of 
awakening. It left me tinghng, as if sparks 
were dancing off my skin. 

Body and Soul 

Thomas improved. He didn't reject his 
father's grafts. And over the next month, 
a researcher at the Massachusetts Insti- 
tute of Technology announced a new 
research method to harvest epidermal 
cells. The patches of skin required for 
this experimental technique were 
exactly like those Thomas still had 
intact. Harvested cells from these 
patches were taken to the laboratory, 
induced to grow, and spread atop a layer 
of denatured collagen. Eventually, the 
cells would coalesce on the collagen 
sheet, which could then be grafted 
directly onto the patient. Since the orig- 
inal cells were all derived from the 
patient, there was no risk of immuno- 
logic rejection. Thomas was among the 
first patients to undergo this procedure. 



His survival was, in effect, the culmina- 
tion of a long sequence of miracles. 

As the months passed, Thomas grew 
strong enough to graduate to Camp 
Chronic. There he endured the usual 
series of surgical revisions. His fingers 
were gone, and his reconstructed hands 
looked like something akin to lobster 
claws. His new nose — constructed of fat 
and muscle from his scalp, then covered 
with a graft patch of skin — ^was more a 
piece of fleshy caulking than elegant 
reconstruction. It covered a terrible gap, 
irreconcilable with our usual notion of 
facial symmetry and composition. But 
Thomas was ahve, against all odds. And 
his spirit was clear and bright. 

If anything, Thomas's spirit shone 
brighter than those of others. He became 
indomitable. Where hundreds of kids 
had faltered, he would not. He was 
adamant about returning to public 
school outside Philadelphia. Then the 
prosthetic shoes on his feet failed. Both 
legs became infected, and he needed to 
have bilateral amputations below the 
knee. It took four more months to learn 
to walk again. But he did, and then he 
asked to return home, back to school. 

It took seven more years to complete 
my neurosurgical training. I didn't see 
Thomas again until the last day of my 
final year as resident. I was on the eleva- 
tor. In the corner stood a horribly disfig- 
ured, diminutive person. I suddenly rec- 
ognized the attractive woman standing 
alongside him. It was Thomas's mother. 

Thomas didn't remember me at all, but 
his mother did. She bragged that he was 
an honor student now. And she wept as we 
departed, teUing me how grateful she was 
for what we had done for him. Thomas 
waved goodbye to me with a misshapen 
hand I had probably helped build. 

But as he waved, he smiled at me. A 
big smile! A real smile! The smile of some- 
one genuinely happy to be ahve. Then I 
realized I had received a great gift on this 
last day of my surgical training. I had 
been brought into a great, full circle. I 
had seen the hell of Crispy Critters. I had 
learned to see beyond the burns and the 



deformities to the real children who hved 
and thrived there. I had been permitted 
to experience the transformational 
moment when the spirit of Thomas's 
father had come from beyond the realm 
of the flesh to intervene, to protect, and 
maybe even to guide us as we took care of 
his son. Now I had been permitted to 
grasp the miracle from beginning to end, 
its entire sweep across time and space. 

As I saw Thomas smile and wave, I 
reminded myself that I had been permit- 
ted to watch the mortal threads of my 
life interweave with the strands of the 
spiritual powers in Thomas's life. The 
trip had lasted precisely the span of my 
eight-year surgical training. That could 
not have been mere coincidence. 

I understood, for the first time, that the 
filaments of my own existence were inex- 
tricably interwoven with Thomas's, his 
father's, his mother's, and those of a host 
of other individuals. An idea began to take 
shape: I could see thousands of orbits, 
mortal and spiritual, all spun from the 
luminous fabric of creation. My eight- 
year-long adventure was not just the story 
of a surgical residency. It was a message: 
We're never sohtary mortal beings. Super- 
natural comfort is all around us — hke the 
spirit of Thomas's father — and never leaves 
us alone without divine strength and pro- 
tection. But without the certainty of our 
link to the supernatural, the burden of our 
individual existence can make us crazy. 
Thomas's experience made me realize that 
suffering is the background, the context, 
against which we discover love's power 
over death, over illness. Suffering is what 
lends love its supremacy over death. ■ 

Allan ]. Hamilton '82 is a professor of neuro- 
surgery and a clinical prof essor in the radiation 
oncology, psychology, and computer and electrical 
engineering departments at the Arizona Health 
Sciences Center in Tucson. This essay was 
excerpted and adapted from Hamilton's most 
recent book, The Scalpel and the Soul: 
Encounters with Surgery, the Supernat- 
ural, and the Healing Power of Hope, hy 
arrangement with Jeremy P. Tarcher, a member of 
Penguin Group (USA) Inc., copyright ©2008. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



51 



In the last years of World War II, 

I played a small part in what may have been one of the largest med- 
ical research projects of that war. Our goal was formidable: to con- 
quer malaria, a disease many thought was unconquerable. We did 
not, unfortunately, achieve that goal. But the story of our project may 
interest, perhaps even encourage, contemporary researchers while 
also providing a picture of the concerns, setbacks, and small tri- 
umphs that were part of what was known as the Malaria Project. 



In the Heat of Battle 

It was apparent early in the war that malaria was 
going to be a scourge to Allied troops, especially 
in their operations in North Africa and the Pacif- 
ic. By 1942, the illness had incapacitated half of 
General Douglas MacArthur's active-duty forces 
in the Southeast Pacific, hobbling the comman- 
der's efforts to advance north from Australia and 
New Guinea. By the war's end, an estimated 
60,000 military personnel had died of malaria in 
those theaters. 

One reason the casualty numbers were high was 
the lack of an available, effective treatment. Prior 
to the war, quinine was the most conmion anti- 



malarial in use. Extracted from the bark of cin- 
chona trees, quinine had originally been harvested 
from wild trees in the jungles of South America. 
Since the eighteenth century, however, the drug 
had been produced from trees cultivated on plan- 
tations throughout Southeast Asia. When this 
region came under Japanese control in the 1940s, 
the world's access to quinine was cut off. 

Synthetic alternatives were limited; quinine's 
effectiveness and low cost had squelched prof- 
itabihty — and thus research — prospects. Although 
there had been some development in the 1930s, 
the results, such candidates as chloroquine and 
atabrine, sat untested on the shelves of manufac- 
turers, including I. G. Farben in Germany and 



)roject aimed at stamping out malaria, by Curtis Prout 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



53 




Winthrop Chemical Company in the 
United States. 

The quinine blockade and the toll 
malaria was taking on U.S. troops spurred 
the U.S. Office of Scientific Research and 
Development, or OSRD, to initiate the 
Malaria Project in 1942. The project 
enlisted a stellar list of U.S. researchers, 
including infectious disease expert 
Lowell Coggeshall and immunologist 
Michael Heidelberger. 

I first learned of the project in Decem- 
ber 1943. 1 was a junior resident at the 
Johns Hopkins Hospital and had been 
summoned to the office of Warfield 
Longcope, the physician-in-chief. 1 was 
nervous, fearing a reprimand for some 
medical error 1 had unknowingly com- 
mitted. But my worries were short-hved 
as Longcope began by telling me of an 
urgent call for researchers ineligible for 
military service and qualified to work 
on a project aimed at finding a cure for 
malaria. Would I be interested? 

1 accepted immediately. I had expected 
to head for the tropics for this research 
but soon learned that decision makers in 
Washington, DC, felt that the factors of 
immunity or partial immunity in areas 
endemic for malaria would interfere with 
the evaluation of any antimalarial med- 
ications. The project's five chnical testing 
areas would instead be stateside. I was 
given a choice between the state prison 
in Joliet, Illinois, and the Boston Psycho- 
pathic Hospital, which was later renamed 
the Massachusetts Mental Health Cen- 
ter. With my wife and our two small 
children in Boston, 1 naturally chose 
the latter. 

The Boston unit was headed by 
Allan Butler '26, a professor of pedi- 
atrics at Massachusetts General Hospi- 
tal, and supported by two senior physi- 
cians at the hospital: Augustus Rose '32 
and Lawrence Trevett. The unit's per- 
sonnel roster was rounded out by three 
young physicians eager to help the war 
effort: Arthur Linenthal '41, Joseph 
Hindle, and me. 



The unit's testing facUities were spht 
between Boston Psychopathic and a 
ward at MGH. At MGH, Linenthal was 
to test and observe any effects of the 
antimalarial candidates on conscien- 
tious objectors who had agreed to work 
at the hospital in heu of being forced into 
the military — or jailed for their refusal. 
At Boston Psychopathic, our unit was to 
test the effectiveness of the antimalarials 
against the disease itseff. Our subjects 
were psychotic patients selected from 
the populations of the dozen or so large 
hospitals overseen by the Massachusetts 
Department of Mental Health. Hindle 
and I were assigned to this hospital. 

The Good, the Bad, and the Ugly 

The idea of using psychotic people as 
test subjects for malaria research was 
ingenious, bizarre, and, especially by 
today's standards, unethical. With 
what justification could we give a dan- 
gerous infectious disease to these peo- 
ple without informed consent? Well, at 
that time there were no ethics commit- 
tees, and a standard for informed con- 
sent in biomedical research had yet to 
be broadly articulated; The Nuremberg 
Code, an outcome of the era's war- 
crimes tribunals, wasn't assembled 
until 1948. 

But there was a sohd scientific ratio- 
nale to this approach. Before penicillin, 
10 percent of aU patients in the mental 
hospitals in the developed world were 



suffering from late syphihs of the brain, 
known as general paresis of the insane, 
or, simply, paresis. Arsenic and bismuth, 
moderately effective in other forms of 
syphilis, did not affect paresis. In Vienna 
in 1917, Juhus Wagner-Jauregg observed 
the effects of malaria on people with 
paresis; some paretics who contracted 
malaria improved greatly. His work 
resulted in cure or improvement for 
many thousands of psychotic paresis 
sufferers and earned him a Nobel prize 
in 1927. At the time, it was thought the 
iUness's fever was effective against pare- 
sis, but later investigations showed the 
effect was probably a result of immunity 
to antigens shared by the treponema of 
syphilis and the malaria parasite. 

By the 1930s, hospitals throughout 
Europe were administering malaria to 
paretic patients with encouraging 
results. In this country, the center for 
malaria therapy for paresis was the Johns 
Hopkins Hospital. By the 1940s, when 
OSRD was deciding how to structure the 
Malaria Project, the malaria treatment of 
paretic patients, in which quinine was 
used to successfully terminate the infec- 
tions, was an accepted standard. 

OSRD studied the procedure and 
approved the use of paretic patients. 
The project was to use an allegedly 
"tame" strain, and quinine was to be 
kept on hand should the experimental 
medications previously tested on the con- 
scientious objectors prove ineffective at 
stemming malarial infections. Although 



54 



HARVARD MEDICAL ALUMNI BULLETIN • AUTUMN 2008 



WHEN THE FEVERS began to cycle every 48 hours 
and the parasite counts reached a predetermined level, we 
would administer an experimental drug that had been 
tested on the conscientious objectors. 



decision makers in Washington may have 
harbored objections to the ethics of this 
approach, the urgency of the wartime 
situation trumped their concerns. 

Into the Breach 



The antimalarial candidates, and even 
the malaria strains we tested on the sub- 
jects in our unit, came out of the research 
laboratories of pharmaceutical compa- 
nies, academic chemistry departments, 
and at least one cosmetic manufacturer. 
Approximately 13,000 candidate com- 
pounds were developed for the project; 
most were hastily tested for toxicity in 
animal models. Malaria strains were also 
tested; avian strains were evaluated in 
domesticated fowl, and human strains 
were tested on dogs and monkeys. The 
outcomes of these trials, unfortunately, 
were rarely shared with the clinicians 
who administered the candidate anti- 
malarial agents. In addition, compounds 
effective against animal malaria were 
usually not effective against the human 
form and vice versa. 

Once we had administered the candi- 
date compounds to our group of consci- 
entious objectors and had inoculated our 
paretic patients with malaria and pro- 
vided them the selected antimalarial, we 
focused on monitoring the effects of the 
agents. Linenthal would monitor his 
charges for changes resulting from the 
antimalarials, and Hindle and I would 
check our patients for disease progres- 
sion after treatment. 

The daily routine at Boston Psycho- 
pathic wasn't arduous. We would carry 
out daily rounds, physical examinations, 
blood counts, and parasite counts for 
which I devised a logarithmic scale for 
charting the daily levels. From time to 
time, one of the senior hospital physi- 
cians, either Rose or Trevett, would come 
by for rounds, and once a week, Butler 
would meet with Linenthal, Hindle, and 
me before departing to Washington to 
report on the results of our testing. 



The testing protocol we followed 
began when we inoculated our paretic 
patients with an attenuated strain of 
Plasmodium vivax, the least virulent of the 
Plasmodia strains to cause malaria. 
When the fevers began to cycle every 48 
hours and the parasite counts reached a 
predetermined level, we would adminis- 
ter an experimental drug that had been 
tested on the conscientious objectors. 
Then we would carefuUy watch parasite 
counts, fever, and the patient's general 
condition. If the disease continued 
unchanged after about a week, we would 
terminate it by giving the patients a dose 
of our closely guarded supply of quinine. 
After a suitable period of observation, 
most patients returned to the state hos- 
pital from which they had come, and we 
never saw them again. 

Even today I am troubled by the fact 
that I never knew what happened to 
those patients. We perpetuated the 
malaria strain we used by taking blood 
from infected patients and injecting it 
intravenously into new arrivals. How 
many patients, I wonder, later developed 
hepatitis or other diseases as a result of 
this practice? And because P. vivax has 
been known to relapse years after its first 
attack, how many suffered subsequent 
attacks — an outcome for which, at the 
time, there was no therapeutic recourse? 

War Stories 



Although at my darkest times I felt I 
wasn't contributing to the war effort, our 
work did produce two scientific papers. 
One was among the first studies to show 
that penicillin was ineffective against 
malaria while another demonstrated the 
effectiveness of penicillin on paresis. 

Some of the more interesting results 
were unpubhshed; they arose from obser- 
vations of the responses that the consci- 
entious objectors had to the various anti- 
malarials. One example stemmed from 
the testing of a compound developed by 
Louis Fieser, a professor of organic chem- 



istry at Harvard College, where he was 
also the chief haison to OSRD. Tests of 
Fieser's products usually were unsuc- 
cessful, and this candidate had been no 
exception. Fieser, however, was unsatis- 
fied with the results and insisted we use 
larger doses for longer periods than our 
protocols permitted. Despite his insis- 
tence, the only effect the compound 
induced was a deep crimson staining of 
the blood plasma, which caused those 
receiving it to look exceptionally pink 
and healthy for several weeks. 

Another compound had a somewhat 
startling side effect; The hair of the 20 or 
so men testing it became white at the 
roots. And their hair continued to grow 
out white until the drug was stopped. 
Thus, some of the conscientious objectors 
developed a broad albino stripe that was 
bordered by their normal hair color — an 
appearance that gained them the nick- 
name "skunks," a moniker that vanished 
when their original hair color grew back. 

Near the end of our project in 1945, 
chloroquine, tested by one of the other 
units, was proving to be marvelously 
effective. We had been simultaneously 
testing its bromine analog. It showed 
itself to be as effective as chloroquine 
against the parasite but more costly and 
less safe, so it was not developed further. 

More than 60 years have passed since 
the Malaria Project ended, and research 
on the disease continues. An estimated 
247 miffion cases of malaria are reported 
globally each year. One million of those 
cases, mostly children under five years, 
die from the disease. It is my hope that 
knowledge of this project may aid sci- 
ence's efforts and ultimately help to con- 
quer what stiU seems unconquerable. ■ 

Curtis Prout '41 taught physical diagnosis at 

Harvard Medical School and Brigham and 
Women's Hospital for many years, served as assis- 
tant dean for students at HMS, and was chief of 
medicine at Harvard University Health Ser- 
vices. Now semi-retired, Prout has an internal 
medicine practice in Manchester, Massachusetts. 



AUTUMN 2008 • HARVARD MEDICAL ALUMNI BULLETIN 



55 




n w 

3 o 
3 



Orq 



CO 



1-:. CO 








z 
n 


LO 




r-t 


< 

Q 




^ 


n 


Q. 


rn 


s 


r-t 


(D 


^ 


Q. 



^ R 
&- ti 



> 
c 
3 

3 



W ►fl C 

en 3 CO 

g 2. T) 

P rt o 



> 



z 
o 

3 

■u 
o 



n 



YOU MUST REMEMBER THIS: 
What can Buddhist monks, medical 
residents, and alien abductees 
tell us about memory? Harvard 
physicians and researchers listen 
so v/e all might learn. 



^> o 

° o 5 

Q 
3^ 

5* 

o 

5' 

3